Abstract: In the last years prevention of temporomandiboular joint (TMJ) disease had acquired great importance. According to the neuro-occlusal rehabilitation (RNO) it is possible to say that TMJ disease starts since first years of life. So it is important both for dentist and for pediatric know what are the conditions and the atypical functions which predispose to this pathology. The aim of this work was to show how it is possible to intercept since primary teeth and the correct norms of primary and secondary prevention.
Abstract: OBJECTIVES: The aim of this study was to investigate mechanisms involved in the growth inhibitory effect of silymarin, in humanhepatocellular carcinoma. MATERIALS AND METHODS: The human hepatocellular carcinoma cell line HepG2 was utilized and the MTT assay was performed to study the antiproliferative effect of silymarin. Dual staining was undertaken for ethidium bromide/acridine orange, propidium iodide staining and DNA fragmentation studies were executed to confirm the presence of apoptosis. Cell-cycle analysis was revealed by flow cytometry and mitochondrial transmembrane potential was measured by uptake of the mitochondrial-specific lipophilic cationic dye rhodamine 123. Western blotting analysis for cytochrome c, p53, Bax, Bcl-2, APAF-1, caspase-3, survivin, beta-catenin, cyclin D1, c-Myc and PCNA was carried out. RESULTS: Silymarin inhibited population growth of the hepatocellular carcinoma cells in a dose-dependent manner, and the percentage of apoptotic cells was increased after treatment with 50 and 75 microg/ml silymarin for 24 h. Silymarin treatment increased the proportion of cells with reduced DNA content (sub-G(0)/G(1) or A(0) peak), indicative of apoptosis with loss of cells in the G(1) phase. Silymarin also decreased mitochondrial transmembrane potential of the cells, thereby increasing levels of cytosolic cytochrome c while up-regulating expression of pro-apoptotic proteins (such as p53, Bax, APAF-1 and caspase-3) with concomitant decrease in anti-apoptotic proteins (Bcl-2 and survivin) and proliferation-associated proteins (beta-catenin, cyclin D1, c-Myc and PCNA). CONCLUSIONS: Our results demonstrate that silymarin treatment inhibited proliferation and induced apoptosis in the human hepatocellular carcinoma cell line HepG2.
Abstract: Craniofacial morphology of patients with nevoid basal cell carcinoma syndrome (NBCCS) has sometimes been reported at clinical examination, but any investigation has described it on the basis of cephalometric measurements.The purpose of this study was to conduct a cephalometric analysis of patients with NBCCS and to compare measurements with non-NBCCS subjects of similar ages, to elucidate if there is any relationship between NBCCS and craniofacial morphology.The study population consisted of 14 adult patients (9 men and 5 women), ranging in age from 18.2 to 56.8 years, with the diagnosis of NBCCS, with good-quality lateral cephalometric radiographs, and 14 adult healthy patients matched for age and sex to the NBCCS group. Cephalometric measurements were carried out on radiographs, and measurements of angles and distances were performed.Statistical differences between NBCCS subjects and controls were observed. Data analysis displayed that the measurements of the anterior cranial base (P <or= 0.0043), mandibular length (P <or= 0.0168), and maxillary length (P <or= 0.0284), posterior facial height (P <or= 0.0406), and of mandibular angle (P <or= 0.0026), facial axis angle (P <or= 0.0402), lower facial height angles (P <or= 0.0135), and of interincisal angulation (P <or= 0.0148) were higher in NBCCS subjects in respect to controls. On the contrary, the facial convexity (P <or= 0.0189) and the mandibular arc angle (P <or= 0.0378) were reduced in NBCCS subjects.According to these findings, NBCCS patients presented a sagittal lengthening of the anterior cranial base and maxilla and a vertically and horizontally overdeveloped mandible, together with the features of a long-face syndrome with a large gonial angle.
Abstract: AIM: The aim of this study was to investigate the relationship between expression of angiogenic and regeneration markers and periodontal disease in subjects with/without diabetes mellitus. MATERIAL AND METHODS: Immunohistochemical detection of vascular endothelial growth factor (VEGF), CD44 and CD133 was performed in 16 samples each of (1) healthy gingiva from non-diabetic subjects (controls), (2) gingiva from non-diabetic subjects with periodontitis, (3) gingiva from subjects with type 1 diabetes and periodontitis, (4) gingiva from subjects with type 2 diabetes and periodontitis. RESULTS: Diseased gingivae from patients with diabetes and periodontitis had greater clinical measures of periodontal disease than those with periodontitis only. VEGF expression was significantly enhanced in epithelial and endothelial cells from patients with periodontitis compared with controls (p<0.05). Epithelial CD44 expression was strong in all groups, while CD44 was significantly enhanced (p<0.05) in connective tissue cells from both diabetic groups. Epithelial and endothelial CD133 expression was comparable in all patients except those with type 2 diabetes and periodontitis, where it was not detected. Stromal CD133 expression was significantly lower in patients with type 2 diabetes and periodontitis and was increased in periodontitis patients (p<0.05). CONCLUSIONS: The involvement and high expression of VEGF, CD44 and CD133 in periodontal disease may predict a greater regeneration capacity of gingival tissue.
Abstract: PURPOSE: Survivin, an inhibitor of apoptosis protein and a cell cycle regulator, has been detected in the majority of human cancers. Five splice variants (survivin, survivin-2alpha, survivin-2B, survivin-3B, and survivin-DeltaEx3) have been identified; their expressions have been investigated here. METHODS: By means of RT real-time PCR and immunohistochemistry, we have evaluated survivin isoform expressions at both mRNA and protein levels in human normal oral tissue, precancerous lesions, and oral squamous cell carcinoma (OSCC). Their correlations with the pathological findings have also been analyzed. RESULTS: Expression levels of all survivin transcript variants were markedly elevated in OSCC when compared to normal tissues. One-way analysis of variance (ANOVA) revealed highly significant up-regulation of survivin (P = 0.001), survivin-DeltaEx3 (P = 0.001) and survivin-2B (P = 0.004), whereas survivin-3B showed a minor increase in OSCC compared to normal mucosa. CONCLUSIONS: Our findings suggest that survivin isoforms deregulation may have significant implications in tumor aggressiveness and prognosis.
Abstract: Cell-cell and cell-matrix interactions regulate important cellular functions; they involve a number of specialised molecules and the corresponding receptors, among which a key role is played by cadherins and the associated catenins. Deregulation of these molecules has been associated with tumour progression in many human malignancies. While catenins expression has been extensively studied in many human cancers, including oral carcinoma (OSCC), less is known about their expression in oral epithelial dysplasia. The objective of this study was to evaluate the expression of these proteins in a large group of displastic lesions of the oral mucosa and their relation with subsequent malignant transformation. Expression of beta- and gamma-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and 10 samples of normal oral mucosa. The presence and absence of beta- and gamma-catenin staining was expressed differently in relation to dysplasia grade; while the degree of dysplasia became more severe, we observed a statistically significant loss and/or reduction of catenins expression, the loss of the exclusive membranous expression and a cytoplasmic delocalisation. Progression to OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed a concurrent and concordantly located beta- and gamma-catenin staining even, if no statistically significant differences were found between cases progressed to invasive OSCC or not. Catenins physiology alterations may be involved in the transformation process; however, the role of catenins expression as possible prognostic markers in precancerous oral lesions seems to be limited. Nonetheless, further studies on larger series of samples are necessary in order to clarify the role of catenins expression in oral carcinogenesis from both a biological and clinical point of view.
Abstract: Fibroblasts play a key role in tissue healing by producing the majority of extracellular matrix components, favouring granulation tissue formation, and stimulating re-epithelialization. Hyaluronan is a component of ECM and its anti-inflammatory effects and properties in enhancing wound closure are well known. In this study, we examined the effects of Aminogam gel, a new pharmacological preparation suggested to improve wound healing, composed of hyaluronic acid, proline, lysine, glycine and leucine, on human fibroblasts. Results show that fibroblasts treated with hyaluronic acid plus aminoacid solution increased their proliferative activity, collagen I and III, and fibronectin synthesis. Moreover, HA plus aminoacid solution increased the expression of transforming growth factor beta, connective tissue growth factor, interleukin-6 and -8, assayed by RT-PCR. These results suggested that Aminogam gel, involved in several stages of wound healing, as fibroblast proliferation, granulation tissue formation, ECM component deposition, and production of cytokines, may be a useful device to favour and accelerate wound closure.
Abstract: Head and neck cancer is the eighth most common cause of cancer death worldwide. Its incidence varies widely among different regions. In North America and the European Union, head and neck cancer accounts for 3% to 4% of all cancer diagnoses. Conversely, in Southeast Asia and Africa, head and neck cancer accounts for approximately 8% to 10% of all cancers1. Although the incidence of head and neck cancers has decreased slightly from 1975 to 2002 in the United States5, approximately 46 000 new cases are still expected in 2007 alone. Even if surgery and radiotherapy have remained the core therapy in squamous cell carcinoma of the head and neck (HNSCC). Radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced (LA-HNSCC) resectable disease. However, some recent developments highlighted the expanding role of chemotherapy, which is increasingly being incorporated in the management of HNSCC. Concurrent chemo-radiotherapy has shown benefits in randomized trials; in addition, chemotherapy is used by itself as palliative therapy for patients with metastatic disease. As our understanding of the molecular and cellular mechanisms involved in cancer development improves, we are better able to identify potential targets for biological therapy and to apply novel strategies to the preclinical study and clinical treatment of head and neck cancers. Current avenues of research, focusing on clinical studies evaluating antibody directed therapies and gene replacement strategies for head and neck cancer are discussed.
Abstract: The immediate placement of dental implants in esthetic areas is a primary challenge for modern implantology. The underlying treatment goal is to preserve the natural periodontal architecture; in recent years, however, a concurrent goal has been to reduce the period between implant placement in the fresh extraction socket and delivery of the definitive restoration, but adequate long-term data are still lacking on the efficacy of this technique. A 3- to 5-year retrospective analysis of 282 dental implants immediately placed into extraction sockets, and temporized with nonoccluding provisional prostheses has been undertaken. All recorded outcomes and complications, as well as a proposed protocol for management of immediate function, are discussed.
Abstract: BACKGROUND: Desquamative gingivitis (DG) is a descriptive term used to indicate epithelial desquamation, erythema, erosions, and/or vesiculobullous lesions of the gingiva. DG is commonly associated with several mucocutaneous disorders and systemic conditions that may carry a poor prognosis and high morbidity; however, there are no clear data concerning the frequency of these disease associations. METHODS: We investigated the epidemiologic features of DG in 125 patients and compared our findings with information from a literature review. RESULTS: In our series, 88% of patients with DG had one of the following three disorders: oral lichen planus (OLP), mucous membrane pemphigoid (MMP), or pemphigus vulgaris. The most common cause of DG was OLP (75% of patients). 22% of patients had isolated gingival involvement, and there were diffuse gingival lesions in 57% of patients. Symptoms ranged from none (1%) to severe pain (10%). There was extra-oral involvement of skin in 14% of patients, conjunctiva in 7%, genital mucosa in 26%, and internal organs in 3%. Our study showed MMP to be associated with DG in only a small percentage of patients (9%); this finding may be related to the patient population, epidemiology of the specific disease, and referral and/or past diagnostic bias. CONCLUSION: Based on our series and recent reports, OLP seems to be the most common cause of DG.
Abstract: Dysphagia, defined as a difficulty in swallowing of fluids and/or solid foods, is one of the most frequent symptoms of esophageal, gastrointestinal, ear, nose and throat diseases. As such, it poses a diagnostic challenge and an interdisciplinary clinical problem. Of particular importance in diagnosis is to distinguish between esophageal and oropharyngeal dysphagia. Oropharyn-geal dysphagia is often associated with neuromuscular disorders and is treated with rehabilitative protocols, while esophageal dysphagia may be due to anatomical alterations and esophageal motility difficulties. While the former can be adequately treated with endoscopic or surgical therapy, the latter are currently treated only pharmacologically. Interestingly, dysphagia may present as the initial symptom of a wide spectrum of oral conditions, including traumatic ulcerations, neuromuscular diseases, systemic and local immuno-mediated or infectious lesions, malignant neoplastic diseases or mucositis following chemo-radiotherapy for head and neck cancers: in these cases it is called oral dysphagia. Dysphagia, with or without evident oral lesions, suggests the presence of an oropharyngeal disease and requires adequate diagnostic-therapeutic management. This paper describes the major oral and systemic diseases that may manifest themselves with oral manifestations inducing dysphagia. Clinical management guidelines in dysphagia triggered by neuromyogenic pathogenesis are discussed.
Abstract: Oral Diseases (2009) doi: 10.1111/j.1601-0825.2009.01617.xObjective: Desquamative gingivitis (DG) represents the gingival manifestation associated with several mucocutaneous disorders and systemic conditions. Little is known of whether or not DG could influence the onset or progression of plaque-related periodontitis. In this study, the potential impact of DG on plaque-related attachment loss and pocket formation has been evaluated. Methods: A cross-sectional evaluation of 12 patients with DG [eight oral lichen planus (OLP), four mucous membrane pemphigoid (MMP)], never treated for DG lesions or plaque-related periodontitis, was carried out. Probing depth (PD), clinical attachment loss (CAL), full-mouth plaque (FMPS), and bleeding (FMBS) scores were evaluated at six sites per tooth. Clinical parameters of sites with DG lesions were compared with that of DG unaffected sites. Results: Median PD and CAL, as well as FMPS and FMBS, were not significantly different (P > 0.05 Mann-Whitney test) for both OLP and MMP patients. However, a negative association between DG lesions and PD < 4 mm (OLP: OR = 0.26; MMP: OR = 0.47), and a positive association with PD 4-6 mm (OLP: OR = 3.76; MMP: OR = 2.68) and with PD > 6 mm (only for OLP: OR = 3.83) were found to be significant. Conclusions: The potential interference between DG lesions and periodontitis needs further prospective investigation; nonetheless, a higher level of attention might be prudent.
Abstract: OBJECTIVE: Langerhans cell histiocytosis (LCH) is a clonal proliferative multisystem disease. Although bone and mucosae have been classified as non-risk organs, their involvement may increase the risk of disease progression. Oral and periodontal lesions are burdened with a significant impairment of quality of life for associated signs, symptoms and loss of function. Most of information regards paediatric disease; the disease in adults has received limited attention. SUBJECTS AND METHODS: A total of 31 adult patients affected by immuno-histopathology confirmed LCH have been prospectively examined; attention was paid to the occurrence and characterization of oral lesions. RESULTS: Twelve patients developed oral lesions. Posterior regions of jawbones were always affected; the involvement of anterior regions was not constant. Unifocal oral involvement was significantly associated with multisystemic disease while multifocal lesions were associated with unisystemic disease. Oral disease presented with soft tissue ulcers (50% of cases), gingival bleeding (66.7%), pain (83.4%), periodontal damage (50%), tooth mobility (16.7%), non-healing extraction socket (8.3%); 41.6% of patients complained of negative outcomes on quality of life. Oral lesions were easily handled with local measures. CONCLUSIONS: Posterior regions require attention; single oral lesions may be part of multisystemic disease; oral and periodontal lesions may be early signs of disease reactivation.
Abstract: BACKGROUND.: Head and neck squamous cell carcinomas (SCCs) are among the most aggressive types of cancer. The Simian virus 40 (SV40), which is a polyomavirus known for its oncogenic potential, was found as a contaminant of oral vaccines and has been related to human pleomorphic adenoma in the parotid gland. The aim of this study was to evaluate the presence of SV40 and 2 human polyomaviruses-BK virus (BKV) and JC virus (JCV)-in a large sample of SCCs of the oral cavity. METHODS.: Quantitative real-time polymerase chain reaction (PCR) was used to evaluate virus load. RESULTS.: Overall, the prevalence of SV40, BKV, and JCV in oral SCC was negligible. Matched-pair case-control analysis indicated that prevalence among the controls did not significantly differ with respect to analyzed cases. CONCLUSION.: The results did not indicate a major role for SV40, BKV, and JCV in the etiology of oral SCC. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.
Abstract: The present study aimed at evaluating, through immunohistochemical staining, E-cadherin, beta-catenin and adenomatous polyposis coli (APC) expression and distribution in normal, dysplastic and neoplastic canine colon and rectum, and at correlating the protein expression with the histological grade of malignancy. In order to obtain a more thorough evaluation of the APC/beta catenin complex, both proteins were also assessed for colocalization in neoplastic cells through double immunofluorescence staining. Immunohistochemical investigation showed a marked decrease of E-cadherin and APC expression in malignant tumours, while a lack of membranous beta-catenin distribution and a cytoplasmic positivity, rather than a decrease of expression, was observed in less differentiated carcinomas. Confocal laser microscopical observation showed cytoplasmic beta-catenin distribution solely in APC-negative cells, demonstrating that the correct beta-catenin distribution on the cell membrane can be APC dependent, as in human colorectal carcinomas. Therefore, the changes in adhesion molecules can play a very important role both in colorectal carcinogenesis and in malignant progression; moreover, these proteins can also be considered powerful prognostic tools in veterinary oncology.
Abstract: The normal articular disc of the human temporomandibular joint (TMJ) consists of regularly arranged collagen fibers and fibroblast-like cells. Disc tissue is subjected to various types of loading. Adaptive remodelling entails microscopic changes in which different types of collagen and non-collagen proteins, as well as matrix metalloproteinases (MMPs), are involved. Collagenase-3 (MMP-13) seems to play a key role. The aim of the study was to evaluate its involvement in TMJ disc histopathology. We studied 10 discs from patients with arthropathy of the TMJ. Paraffin wax-embedded sections were processed for histological and immunohistochemical analysis. A well-characterized mouse monoclonal anti-MMP-13 antibody (anti-collagenase 3) was used. The results showed increased MMP-13 immunoreactivity in TMJ diseased disc tissue was correlated with the severity of the histopathological changes. The more severe the pathological changes, the greater the number of immunolabelled cells detected. Nearly all chondrocyte-like cells were immunopositive, whereas fibroblast-like cells and fibrochondrocytes were more rarely labelled. MMP-13 upregulation in disc tissue from patients with TMJ internal derangement suggests that MMP-13 is involved in disc histopathology, and that disc cells actively participate in the synthesis of extracellular matrix-degrading proteinases.
Abstract: OBJECTIVES: Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. STUDY DESIGN: Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. RESULTS: Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). CONCLUSIONS: Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.
Abstract: Parotidectomy is the most common approach for benign salivary neoplasms. The aim of the present study was to retrospectively analyse no. 34 extracapsular lumpectomies (ELs) performed with superficial musculoaponeurotic system (SMAS) flaps on 32 patients for benign parotid tumours. Based on the extent of the surgical defect the surgical resection was associated with sternocleidomastoid (SCM) muscle rotation flap in 8 patients, superficial temporal artery fascial flap (STAFF) in 2, and temporalis muscle rotation flap in 2. None of the patients affected by pleomorphic adenoma or Warthin's tumour had a complete facial palsy. Only 1 patient (2.9%) had a postoperative transient partial facial paralysis with incomplete eye closure. Neither haematoma formation, nor wound infection was observed, while seroma formation occurred in only 1 patient (2.9%). No cases of Frey's syndrome occurred. An SMAS flap should be performed in primary postparotidectomy reconstruction; a temporoparietal fascia flap (TPFF) if a major defect is anticipated, or when the SMAS has to be resected; an SCM muscle flap covered by an SMAS flap is the method of choice in more extensive rare defects.
Abstract: OBJECTIVES: The protective role of saliva in the case of oesophageal exposition to gastric acid has long been studied but some contradictions still remain. The main end-point of this study was to evaluate if a qualitative and quantitative alteration in salivary secretion exists in patients affected by GERD. METHODS: One hundred and twenty patients (T group) with clinically and endoscopically diagnosed GERD, and 98 healthy subjects (C group) have been evaluated; salivary tests (i.e. basal flow rate, stimulated flow rate, pH, [Na(+)] and [K(+)]) were performed, socio-demographical variables and oral GERD-related symptoms were taken into account. SPSS 10.5 software was used for statistical univariate and multivariate analyses. RESULTS: GERD patients and controls were found to have a similar basal flow rate but different stimulated salivary function [T group mean value 0.989 ml/min (+/-0.48718) vs. C group 1.2197 ml/min (+/-0.6108), pH [T group mean value 8.935 (+/-0.471) vs. C group 7.879 (+/-0.526)] and a higher K(+) concentration. In GERD patients we also registered a significant association with xerostomia [69/120 (57.5%) vs. 28/98 (28.7%)] and an oral burning sensation [58/120 (48.3%) vs. 19/98 (19.3%)]. CONCLUSIONS: Our findings assess that salivary secretion is altered in GERD patients and highlight the need for further investigations in order to define the role of saliva in the etiopathogenesis of GERD.
Abstract: OBJECTIVE: To assess the occurrence of oral pathological changes and symptoms in patients affected by gastro-oesophageal reflux disease (GERD). PATIENTS AND METHODS: 200 patients with GERD and 100 matched healthy controls were studied. Thorough visual examination of the dental and oral mucosal tissues was performed and medical history relevant to oral symptoms was collected. The primary outcome was defined as a statistically significant difference, between the study group and controls, in the presence of the following indicators: soft/hard palate and uvula erythema, tooth wear, xerostomia, oral acid/burning sensation, subjective halitosis and dental sensitivity. Statistical analysis included chi-squared test, and crude odds ratio with 95% CI. RESULTS: Univariate analysis showed that xerostomia, oral acid/burning sensation, subjective halitosis, and soft and hard palate mucosa and uvula erythema were more common in patients with GERD than matched controls (P < 0.05). CONCLUSIONS: This study failed to find any significant association between GERD and dental erosions, whereas some symptoms and other objective oral mucosal changes were found to be significantly associated with GERD.
Abstract: Zirconium oxide (ZO) has outstanding mechanical properties, high biocompatibility and high resistance to scratching. Since dental implants are made with ZO and the genetic effects of ZO on osteoblasts are incompletely understood, we used microRNA microarray techniques to investigate the translation process in osteoblasts exposed to ZO. By using miRNA microarrays containing 329 probes designed from Human miRNA sequences, we identified in osteoblast-like cells line (MG-63) cultured on ZO disks several miRNA whose expression was significantly modified. The most notable regulated genes acting on osteoblasts are: NOG, SHOX, IGF1, BMP1 and FGFR1. The data reported below represent the first study on translation regulation in osteoblasts exposed to zirconium and one in which the effect of ZO on bone formation has been detected.
Abstract: BACKGROUND: MicroRNAs (miRNAs) are a class of small, functional, noncoding RNAs of 19 to 23 nucleotides which induce degradation of specific messenger RNAs (mRNAs), thus controlling the translational process (ie, synthesis of proteins from mRNAs). In addition, mRNAs regulate the promoter of specific miRNAs activating an autoregulatory feedback loop. PURPOSE: Titanium and zirconium dioxide ceramics (ZDCs) are used to make dental implants. Because the molecular mechanism by which ZDC and Ti act on osteoblasts is incompletely understood, we attempted to get more information by comparing the effect of ZDC and Ti on osteoblast miRNAs. MATERIALS AND METHODS: By using miRNA microarray technique, we identified in osteoblast-like cell line (MG63) grown on grade 3 Ti and ZDC disks several miRNAs whose expression was modified. We collected mRNAs after 24 hours of cell culturing to better understand molecular events related to early bone healing around inserted implants. An mRNA microarray technique was then performed as a control. RESULTS: There were six up- and four down-regulated miRNAs. Because every miRNA regulates hundreds of genes, we focused only on those related to bone formation. Among them, the most notable are BMP4 and 7, which are both up-regulated in osteoblasts cultured on Ti disks. CONCLUSION: The detected miRNAs differentially expressed in osteoblast-like cells grown on ZDC versus Ti act on a limited number of miRNAs and bone-related genes. The most notable are BMP4 and 7, which are more expressed in osteoblasts exposed to Ti surface. Consequently, we suggest that Ti surfaces could provide some advantages to immediate load implantology.
Abstract: BACKGROUND: Saliva is one of the most promising and easy-to-collect source of potential biomarkers of oral and systemic disease. We standardized a protocol suitable for pre-analytical treatment and for the analysis of whole normal saliva by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF/MS). METHODS: We evaluated the impact of storage time, freeze/thaw cycles, denaturing agents, glycoproteins depletion, centrifugation, type of matrix and ProteinChip used on the quality of the SELDI protein profile. Moreover, we explored the inter-individual and between-sex differences and the changes in the sample composition over the day. RESULTS: Saliva was qualitatively stable, in the absence of protease inhibitors, for up to 3 h from the collection at room temperature, although the intensity of a number of peaks slightly decreased between 0 and 3 h and the addition of protease inhibitors did not completely revert this trend. The saliva proteome changed during the day and showed relevant between-sex differences. The protein profile remained stable for up to five freeze/thaw cycles. The addition of denaturing solutions and the depletion of glycoproteins improved the quality of the spectra without affecting their reproducibility. CONCLUSIONS: We defined a protocol that improved the quality and the reproducibility of SELDI-TOF/MS analysis, thus potentially supporting the search for putative biomarkers of disease.
Abstract: Nodular fasciitis is an uncommon tumor-like fibroblastic proliferation that occurs rarely in the head and neck region. A new case of nodular fasciitis occurring in the cheek of a 56-year-old woman is reported. The case was characterized by dental trauma preceding the appearance of the lesion (extraction of tooth 35). Histologically, the lesion consisted of proliferating fibroblasts and myofibroblasts presenting clinically as a rapidly growing subcutaneous nodule. A conservative surgical excision with curettage is the treatment of choice, and the lesion usually does not exhibit a tendency to recur. The clinical relevance of this condition relies on the fact that both the disorder and its surgical treatment may cause tissue distortion resulting in aesthetic compromise. Furthermore, it needs to be differentiated from malignancy due to its very rapid growth, its rich cellularity, and its high mitotic activity. Both of these aspects, i.e. aesthetic implications and differential diagnosis, have been discussed.
Abstract: AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.
Abstract: The term desquamative gingivitis (DG) refers to a clinical manifestation that can be caused by several disorders. Many of them are immunologically mediated; in addition to the oral cavity, they can affect extraoral mucocutaneous sites, e.g., larynx, conjunctiva, esophagus, nasal and genital mucosa, and the skin. The degree of oral, periodontal, and systemic involvement determines the overall morbidity and, sometimes, the mortality of these disorders. We comprehensively review disorders commonly associated with DG and highlight diagnostic pathways, guidelines for differential diagnosis, and oral, periodontal, and systemic implications. More rare conditions are reviewed as well. Mucous membrane pemphigoid, oral lichen planus, and pemphigus vulgaris are responsible for the majority of cases of DG. In addition, other uncommon disorders should be considered. Accurate clinical, histologic, and serologic investigations are often required to differentiate among DG-associated disorders, provide adequate therapy, and improve the prognosis of patients.
Abstract: INTRODUCTION: Contrary to early beliefs, celiac disease (CD) is relatively common; however, it still remains underdiagnosed since most cases are atypical, with few or no gastrointestinal symptoms and predominance of extraintestinal manifestations. As a consequence, the diagnosis of the disorder often requires a multidisciplinary approach. Also some oral ailments have been described in celiac patients. In this study, we review the papers that have reported oral manifestations in subjects with CD. METHODS: A comprehensive literature search was conducted in Medline and Embase databases using appropriate key words. Additional papers were selected by cross-referencing from the retrieved articles. RESULTS: Dental enamel defects are the oral lesions most closely related to CD. There are conflicting data on the association between CD and recurrent aphthous stomatitis. A correlation of CD with atrophic glossitis has been reported, although robust evidence in support of it is lacking. Patients with CD have caries indexes seemingly lower than healthy individuals, but they may experience delay in tooth eruption. Occurrence of other oral mucosal lesions in CD subjects is likely occasional. CONCLUSIONS: Patients with systematic dental enamel defects should be screened for CD even in the absence of gastrointestinal symptoms. CD screening tests for patients with oral aphthae or idiopathic atrophic glossitis should be selectively considered during a medical evaluation that focuses on all aspects of the patient's status.
Abstract: OBJECTIVE: To assess a panel of risk factors associated to oral candidosis (OC) onset and its chronic maintenance by means of fuzzy logic (FL) approach and statistical traditional methodology (STM); to investigate their casual relationship within a multifactorial framework. DESIGN: Case-control study. SETTING: One hospital-based clinic. PATIENTS: Eighty-nine patients with OC infection microbiologically diagnosed and 98 healthy subjects were consecutively recruited. OUTCOME MEASUREMENTS: Anamnestic and clinical evaluations for OC, microbiological assessment (i.e. culture, CFU/mL counting and identification) were performed. The commonest predisposing factors for OC onset and its chronic status were analysed by FL and STM. RESULTS: By means of a twofold analysis (FL and STM) significant associations between OC onset and its chronic maintenance were found with respect to denture wearing and hyposalivation/xerostomia, as local risk factors, and to age and female gender, as socio-demographical variables. Tobacco smoking was found not to be a risk factor. CONCLUSIONS: The twofold (FL and STM) statistical approach for the identification of OC risk factors has been found useful and accurate in individuating a more selected target population for OC onset and chronic maintenance. The target patient appears to be an elderly person with multiple disease inducing, directly or by medications, hyposalivation/xerostomia. This data could provide to general and dental practitioners a decision-making model finalised to their preventative strategies for the geriatric population.
Abstract: Subepithelial vesiculobullous conditions are chronic autoimmune disorders that arise from reactions directed against components of the hemidesmosomes or basement membrane zones (BMZ) of stratified squamous epithelium to which the term immune-mediated subepithelial blistering diseases (IMSEBD) has been given. Mucous membrane pemphigoid (MMP) is the most common, but variants do exist. Non-immune disorders that involve these epithelial components typically have a genetic basis--the main example being epidermolysis bullosa. All subepithelial vesiculobullous disorders present as blisters and erosions, and diagnosis must be confirmed by biopsy examination with immunostaining, sometimes supplemented by other investigations. No single treatment reliably controls all subepithelial vesiculobullous disorders; the immunological differences within IMSEBD may account for differences in responses to treatment. Currently, as well as improving oral hygiene, immunomodulatory treatment is used to control the oral lesions of MMP, but it is not known if its specific subsets reliably respond to different agents.
Abstract: The aim of our study is to investigate the effects of chronic sacral neuromodulation on Nitric Oxide (NO) metabolism in the rat bladder. 26 female Sprangue-Dawley rats were considered: group I, normal control rats; group II, a sham treatment, in whom catheters for electrical stimulation were placed in the S1 foramen bilaterally and left in place for 21 days, without performing neuromodulation; group III in whom electrical sacral neuromodulation was performed for 21 days. Finally a cystectomy was performed and the bladder biopsy specimens were sent for immunostaining with n-NOS and i-NOS. Morphological and immunohistochemical analysis was carried out, and evaluated in urothelial cells, endothelial cells and muscle fibers of the muscularis propria. Differences between the 3 groups were analyzed by Student Newman-Keuls test. We could observe that urothelial and endothelial i-NOS (37.00+/-4.69 and 59.00+/-7.42 respectively) and urothelial n-NOS (36.80+/-7.85) expression are significantly increased in neuromodulated rats, compared to groups 1 and 2 (p<0.005). In conclusion, the increase of i-NOS expression on endothelial cells after sacral neuromodulation could be in some way related to angiogenetic responses in the microvascular structures; the increase of n-NOS and i-NOS expression on urothelial cells can suggest that NO is able to influence the plasticity of bladder response, inducing the release of messengers within the urothelium. This study can therefore improve our understanding of the mechanisms of sacral neuromodulation on chronic bladder dysfunction; further studies will need to better demonstrate the role of angiogenesis in the bladder after sacral neuromodulation and to investigate the effects of neuromodulation in rats with chronically induced bladder dysfunction.
Abstract: Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer.
Abstract: Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5-10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic therapy and topical chemotherapy. Radiotherapy should be avoided. Vitamin A analogs may play a preventive role against development of new BCCs. Life expectancy in NBCCS is not significantly altered but morbidity from complications can be substantial. Regular follow-up by a multi-specialist team (dermatologist, neurologist and odontologist) should be offered. Patients with NBCCS should strictly avoid an excessive sun exposure.
Abstract: Deregulated expression of inhibitors of apoptosis may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to chemo- and radiotherapy. In this study, we have investigated, by immunohistochemical technique, the expression and potential prognostic significance of survivin in a series of 49 clear cell type renal cell carcinoma (ccRCC). Survivin expression was significantly associated with poorly differentiated, advanced stages and more aggressive ccRCCs (p < 0.05). Patients with low survivin expression had statistically significant better survival rates than patients with high survivin expression (p < 0.05). This may be relevant for follow-up protocols design and/or alternative therapeutic approaches.
Abstract: PURPOSE: Peptide-15 (P-15) is an analog of the cell-binding domain of collagen. P-15 has been shown to facilitate physiological process in a way similar to collagen, to serve as anchorage for cells, and to promote the binding, migration, and differentiation of cells. However, how P-15 alters osteoblast activity to promote bone formation is poorly understood. We therefore attempted to address this question by using microarray techniques to investigate the microRNA (miRNA) expression in osteoblasts exposed to P-15. MATERIALS: The miRNA oligonucleotide microarray provides a novel method to carry out genome-wide miRNA profiling in human samples. By using miRNA microarrays containing 329 probe designed from human miRNA sequence, we identified in osteoblast-like cells line (MG-63) cul-tured with P-15 several miRNA whose expression is significantly modified. RESULTS: We identified 11 up-regulated miRNA (i.e., mir-337, mir-15b, mir-377, mir-100, mir-148a, mir-125a, mir-199a, mir-221, mir-let-7d, mir-92, mir-23b) and six down-regulated miRNA (i.e., mir-422a, mir-19a, mir-224, mir-145, mir-22, mir-29a). CONCLUSION: The data reported are, to our knowledge, the first on translation regulation in osteoblasts exposed to P-15. They can be relevant to better understand the molecular mechanism of bone regeneration and can serve as a model for comparing other materials with similar clinical effects.
Abstract: A possible relationship between periodontal diseases (PDs) and cardiovascular diseases (CVDs) has been supposed and investigated. This review of the literature focuses exclusively on published studies on current theories and models of correlation between PDs and CVDs. A literature search of clinical and observational studies, in the English language, was performed in MEDLINE/PubMed, OVID database and Cochrane Oral Health Group's Trial Register. In addition, references cited in reviewed studies were evaluated for relevant papers. Various mechanisms are described in order to explain this possible association such as a hyper-responsive inflammatory response to chronic infections in predisposed individuals, and systemic effects of periodontal microorganisms including blood platelet aggregation, atheroma formation, increase in lipid levels, activation of acute phase reaction and systemic production of proinflammatory mediators, but a ultimate relation as well as the potential mechanisms have not been defined yet. Controversial result can be related to different method or objectives of studies including different study design, exposure evaluation, outcome variables and clinical endpoints considered. This paper provides a narrative review of the epidemiological studies dealing with the potential association between PDs and cardiovascular events. A precise association between PDs and CVDs, as well as the involved mechanisms are not yet well defined. Additional large-scale longitudinal epidemiological and intervention studies are necessary to validate this association.
Abstract: Metastatic tumours to the oral region are rare, and those reported in the buccal soft tissues are even less frequent. We describe a case of anaplastic carcinoma of the lung in a 60-year-old man, presenting a huge oral metastasis as the first sign of his primitive lung malignancy. Clinically, the oral lesion mimicked a high-grade primitive carcinoma of the oral cavity. The biopsy established the gingival metastasis from lung cancer which was confirmed by a fine-needle aspiration cytology examination. We report an uncommon case of metastatic lung carcinoma to the gingiva emphasizing the differential diagnosis between primary and metastatic tumours; a short discussion on the pathways of metastatization to oral cavity soft tissues, as well as brief review of the literature are also presented.
Abstract: Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naive lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.
Abstract: Titanium is the criterion standard among materials used for prosthetic devices because of its good mechanical and chemical properties. When exposed to oxygen, titanium becomes an oxide that is biocompatible and able to induce osseointegration. There are 3 allotropic forms of titanium dioxide: brookite, rutile, and anatase. Anatase can be prepared as a colloidal suspension and then used to coat surfaces. Anatase coating (AC) can potentially have specific biologic effects and specifically induce bone formation. To get more information as regards the osteogenic effect of AC, we used microRNA (miRNA) microarray techniques to investigate translation regulation in osteoblasts exposed to AC. Transduction, transcription, and translation are the 3 levels of regulation of cell activity. Recently, a new type of translation regulation has been identified: RNA interference. RNA interference is a process in which miRNA (i.e., noncoding RNAs of 19-23 nucleotides) can induce sequence-specific mRNA degradation and/or translational repression. The human genome encodes a few hundred miRNAs that can posttranscriptionally repress thousands of genes. miRNA oligonucleotide microarray provides a novel method of carrying out genome-wide miRNA profiling in human samples. By using miRNA microarrays containing 329 probes designed from human miRNA sequences, we identified in osteoblast-like cell line (MG-63) cultured with AC several miRNA whose expression had been significantly modified. The data reported constitute, to our knowledge, the first study on translation regulation in osteoblasts exposed to AC. They can be relevant to a better understanding of the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.
Abstract: BACKGROUND: Eating disorders (ED) are a group of psychopathological disorders affecting patient relationship with food and her/his own body, which manifests through distorted or chaotic eating behavior; they include anorexia nervosa, bulimia nervosa and ED not otherwise specified and may be burdened with life-threatening complications. As oral manifestations of ED can occur in many phases of disease progression, they play a significant role in assessment, characterization and prognosis of ED. METHODS: Mucosal, dental, and salivary abnormalities associated with ED have been reviewed. Relations between oral menifestations and pathogenesis, management and prognosis of ED have been critically analysed. RESULTS: Oral manifestations of ED include a number of signs and symptoms involving oral mucosa, teeth, periodontium, salivary glands and perioral tissues; differences exist between patients with anorexia and bulimia. Oral manifestations of ED are caused by a number of factors including nutritional deficiencies and consequent metabolic impairment, poor personal hygiene, drugs, modified nutritional habits and underlying psychological disturbances. CONCLUSION: Oral manifestations of ED can cause impairment of oral function, oral discomfort and pain, and an overall deterioration of aesthetics and quality of life. Their treatment can contribute to overall patient management and prognosis.
Abstract: INTRODUCTION: In the literature, there exists a wide range of human papillomavirus (HPV) DNA prevalence for head and neck squamous cell carcinoma (HNSCC), especially in relation to methods of viral detection and the lesion site. We estimated the pooled prevalence of HPV DNA in biopsies of HNSCC generically grouped versus oral squamous cell carcinoma (OSCC) in relation to the method of viral DNA detection, with the primary end point of verifying if these two variables (specification of tumour site and method of HPV DNA identification) influence the datum on HPV assay. METHODS: By means of MEDLINE/PubMED/Ovid databases, we selected studies examining paraffin-embedded (PE) biopsies of HNSCC and OSCC. According to the inclusion criteria, 62 studies were analyzed. The following data were abstracted: sample size, HPV DNA prevalence, methods of detection [PCR and in situ hybridization (ISH)] and HPV genotypes. After testing the heterogeneity of the studies by the Cochran Q test, metanalysis was performed using the random effects model. RESULTS: The pooled prevalence of HPV DNA in the overall samples (Sigma: 4852) was 34.5%, in OSCC it was 38.1% and in the not site-specific HNSCC was 24.1%. With regard to the detection method, PCR-based studies reported a higher prevalence rate than ISH-based rates (34.8, versus 32.9%) especially in the OSCC subgroup (OSCC PCR based: 39.9%). CONCLUSION: These findings support the assumption that a correct distinction of HNSCC by site, together with the use of more sensitive HPV DNA detection methods, should be considered as essential prerogatives in designing future investigations into viral prevalence in head and neck tumors.
Abstract: Calcium sulfate (CaS) is a highly biocompatible material and enhances bone formation in vivo. However, how CaS alters osteoblast activity to promote bone formation is incompletely understood. We therefore investigated the translation regulation in osteoblasts exposed to CaS by using microRNA microarray techniques. Transduction, transcription, and translation are the three levels of regulation of cell activity. Recently, a new type of translation regulation has been identified: RNA interference (RNAi). RNAi is a process in which microRNA, (miRNA), that is, noncoding RNAs of 19-23 nucleotides can induce sequence-specific mRNA degradation and/or translational repression. The human genome encodes a few hundred miRNAs that can post-transcriptionally repress thousands of genes. The miRNA oligonucleotide microarray provides a novel method of carrying out genome-wide miRNA profiling in human samples. By using miRNA microarrays containing 329 probes designed from Human miRNA sequences, we identified in osteoblast-like cells line (MG-63) cultured with CaS (Surgiplaster, Classimplant, Roma, Italy) several miRNA whose expression is significantly modified. The data reported are, to our knowledge, the first study on translation regulation in osteoblasts exposed to CaS. They could be relevant to a better understanding of the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.
Abstract: INTRODUCTION: Recent studies have demonstrated the capacity of the human organism to prevent the growth of potentially carcinogenic cells by paralyzing them. This antitumor mechanism is known as cellular senescence and is defined as an emergency defence system for cells on the way to becoming cancerous. RESULTS: This review of the literature suggests that oncogene-induced senescence may be a response to oncogenic activation, acting as a natural barrier against tumorigenesis at a premalignant stage. Thus, a large number of cells enter senescence in premalignant lesions but none do so in malignant tumors, due to the loss of senescent pathway effectors such as p16(INK4a) or ARF-p53. Potential senescence markers in oral precancerous lesions include p21(WAF1), p16(INK4a), pRb, Maspin, RAR-beta, G-actin, p15(INK4b), DCR2, and DEC1, some of which are currently under study. CONCLUSION: In the short term, the study of this mechanism may yield valuable data for the management of oral cancer and precancer, for which no effective diagnostic or prognostic markers are yet available.
Abstract: Titanium is a highly biocompatible material and very osteogenic in vivo. However, how titanium regulates osteoblast activity to promote bone formation is incompletely characterized. We, therefore, attempted to get more information by using microRNA (miRNA) microarray techniques to investigate translation regulation in osteoblasts grown on titanium disks. The miRNA oligonucleotide microarray provides a novel method to carry out genome-wide miRNA profiling in human samples. By using miRNA microarrays containing 329 probes designed from the human miRNA sequence, several miRNA were identified in osteoblast-like cell line (MG 63) grown on titanium disks. There were 13 upregulated miRNAs (ie, mir-23a, mir-222, mir-523, mir-22, mir-23b, mir-143, mir-377, mir-24, mir-422b, mir-26a, mir-29a, mir-17-5p, mir-182) and 2 down-regulated miRNAs (ie, mir-187, mir-339). The data reported are, to our knowledge, the first study on translation regulation in osteoblasts exposed to titanium. The data can be relevant to understand better the molecular mechanism of osteoblast activation and as a model for comparing other materials with similar clinical effects.
Abstract: BACKGROUND: Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia. METHODS: In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate. RESULTS: In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives. CONCLUSION: The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients.
Abstract: BACKGROUND: A close correlation between celiac disease (CD) and oral lesions has been reported. The aim of this case-control study was to assess prevalence of enamel hypoplasia, recurrent aphthous stomatitis (RAS), dermatitis herpetiformis and atrophic glossitis in an Italian cohort of patients with CD. METHODS: Fifty patients with CD and fifty healthy subjects (age range: 3-25 years), matched for age, gender and geographical area, were evaluated by a single trained examiner. Diagnosis of oral diseases was based on typical medical history and clinical features. Histopathological analysis was performed when needed. Adequate univariate statistical analysis was performed. RESULTS: Enamel hypoplasia was observed in 26% cases vs 16% in controls (p > 0.2; OR = 1.8446; 95% CI = 0.6886: 4.9414). Frequency of RAS in the CD group was significantly higher (36% vs 12%; p = 0.0091; OR = 4.125; 95% CI = 1.4725: 11.552) in CD group than that in controls (36% vs 12%). Four cases of atrophic glossitis and 1 of dermatitis herpetiformis were found in CD patients vs 1 and none, respectively, among controls. CONCLUSION: The prevalence of enamel hypoplasia was not higher in the study population than in the control group. RAS was significantly more frequent in patients with CD.
Abstract: Ulcers and/or erosions can be the final common manifestation, often clinically indistinguishable, of a wide and complex spectrum of conditions including traumatic lesions, infectious, vesiculo-bullous, neoplastic and gastrointestinal diseases. Their formation represents the final outcome of a complex and finely orchestrated phenomenon involving both epithelial lining and chorion. Reduction of blood flow, cytokine production, cell death, wound repair, all participate to the dynamic process which we define as ''ulcer''. However, little is known about the mechanisms which crucially contribute in determining the phenomenology of ulcer, and some questions still remain unsolved. This paper aims to explain the pathophysiology of oral ulcers attempting to answer three questions: the mechanism of ulcer development, the site of appearance, and the factors which determine the severity and healing time of ulcerative lesions.
Abstract: AIMS: Squamous cell carcinoma (SCC) of the tongue shows aggressive behaviour and a poor prognosis. Clinicopathological parameters fail to provide reliable prognostic information, so the search continues for new molecular markers for this tumour. Chromatin assembly factor-1 (CAF-1) plays a major role in chromatin assembly during cell replication and DNA repair and has been proposed as a new proliferation marker. The aim of this study was to investigate its expression in SCC of the tongue. METHODS AND RESULTS: The immunohistochemical expression of the p60 and p150 subunits of CAF-1 were evaluated in a series of SCCs of the tongue. The findings were correlated with the expression of proliferation cell nuclear antigen (PCNA) and patients' clinicopathological and follow-up data. CAF-1/p60 was expressed in all the tumours, whereas CAF-1/p150 was down-regulated in a number of cases. Overexpression of CAF-1/p60 and down-regulation of CAF-1/p150 identified SCCs with poor outcome, in addition to the classical prognostic parameters. CONCLUSIONS: Simultaneous CAF-1-mediated deregulation of cell proliferation and DNA repair takes place in aggressive SCC of the tongue. Therefore, the evaluation of CAF-1 expression may be a valuable tool for evaluation of the biological behaviour of these tumours. This may be relevant to the introduction of improved follow-up protocols and/or alternative therapeutic regimens.
Abstract: Surgery, chemotherapy and radiotherapy are different therapeutical options for the management of the head and neck cancers. Their indication is strictly relate to some parameters (macro and microscopic characteristics of the tumor, the patient's general health and the remaining expectations of the life of the patients). Surgical treatment of the cancer, even if it represents the most radical approach and with the most therapeutical index, it always can't be practicable, since, often, it is associated to imposing aesthetical and functional alterations of the interested district. Chemotherapic agents are among the drugs with the lower therapeutical index, that are able to cause side effects, mainly due to the immunosuppression. About radiations, side effects could be indicates as immediates or acutes, and backward or chronic. Among the acute manifestations are enumerated: xerostomia, mucositis, bacterial infections, dysgeusia, dysphagia; among chronic forms: hyposalivation-xerostomia, caries, telangiectasis, infections, osteoradionecrosis, trismus, muscular fibrosis, necrosis of the soft tissues. Mucositis and xerostomia are the most common side effects, and they are a potential source of life-threatening infections. Few interventions are of proven efficacy to reducing severity and duration of mucositis, and there are no universally accepted treatment protocols, but research activity is increasing because of the upward recognition of the importance of mucositis, that need a complex and multidisciplinary clinical management.
Abstract: The topic of this study is the impact of several pre-analytical and analytical variables on proteomic profiling of human urine by surface enhanced laser desorption/ionization time of flight-mass spectrometry (SELDI-TOF-MS) in healthy subjects. Urine storage at room temperature caused a progressive degradation of proteins, which was prevented by the addition of protease inhibitors only up to 2 h from the collection. The timing of collection over the day had only a minor impact on protein profile, although influencing the intensity of peaks. Repeated freeze/thaw cycles (up to five) did not affect either the number or the intensity of the peaks. A comparison of the protein profile from eight different healthy individuals showed fairly consistent inter-subject similarities, along with between-subject differences, which were markedly dependent on the sex and the type of ProteinChip array used. The addition of a variety of denaturing agents improved the quality of the spectra with all the chips tested (CM10, Q10 and H50), but not with the copper-coated IMAC-30 chip. Finally, SPA matrix allowed to achieve a better performance of SELDI-TOF/MS spectrum, as compared with CHCA, regardless of the ProteinChip array used and even in the low m/z range (2500-10,000). In conclusion, we suggest that a careful choice of a number of pre-analytical and analytical conditions is required to accomplish and define a unifying protocol for the analysis of human urine by SELDI-TOF/MS, in physiological and in pathological states.
Abstract: Titanium is the gold standard among materials used for prosthetic devices because of its good mechanical and chemical properties. There are three allotropic forms of titanium dioxide: brookite, rutile, and anatase. Anatase can be prepared as a colloidal suspension and used to coat surfaces. Anatase coating (AC) can potentially have biological effects and specifically can induce bone formation. To obtain more information about the osteogenic effect of AC in comparison to to titanium we used microRNA (miRNA) microarray techniques to investigate the translation regulation in osteoblasts exposed to both titanium and AC. There were three upregulated miRNAs (mir-1, mir-34c, mir-210) and eight downregulated miRNAs (mir-23b, mir-377, mir-22, mir-93, mir-422b, mir-17-5p, mir-24, mir-130b) for false discovery rate = 0 and score >3. The data reported are relevant to understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.
Abstract: We present a new treatment algorithm aimed to assist surgeons to develop a rational diagnostic protocol and establish effective conservative surgical management in patients with mandibular ameloblastoma. Fifteen consecutive cases treated by conservative management were reviewed. Data collected included age, sex, symptoms and signs at diagnosis, anatomical distribution of the lesions, numbers and types of operations, number of recurrences, and duration of follow-up post-operatively. Curettage was the first operation for all patients and they were closely followed-up post-operatively. During the follow-up period (4-10 years), small recurrences were diagnosed early in 7 patients who were treated by radical surgery including marginal or "box" resection. No further recurrences were observed after the second operation. When detected early, recurrences are small and surrounded by a large amount of uninvolved normal bone so it is possible to manage them with a radical resection, so lowering the risk of further recurrence and avoiding severe cosmetic and functional problems.
Abstract: BACKGROUND: Chronic desquamative gingivitis (DG) is a condition characterized by erythema, ulceration, and desquamation of the free and attached gingiva, usually expression of a district-systemic disease, such as oral lichen planus (OLP). METHODS: A combined protocol of oral hygiene and topic corticosteroid therapy was applied in 30 patients with DG associated with OLP. Plaque index (PI) and bleeding on probing (BoP) were evaluated at baseline and after 3 months. RESULTS: PI scoring was significantly lower after treatment in anterior, posterior, and all sites (P < 0.0001) as well as in vestibular and lingual ones (P < 0.0001 and P = 0.0001, respectively). BoP measures were found to be reduced significantly to 22.94% in a full-mouth evaluation (P < 0.0001; OR = 2.633; 95% CI: 2.2685-3.0561) as well as in each specific site (P < 0.0001). CONCLUSION: This clinical trial validated the efficacy, in patients with DG associated with OLP, of a protocol based on professional oral hygiene and self-performed plaque control measures in improving of gingival health status.
Abstract: Severe gingival overgrowth is one of the most frequent side effects in renal transplant patients associated with assumption of cyclosporine A. Several associations with age, sex, dosage, duration of therapy or interval since transplantation have been hypothesized. The introduction of alternative immunosuppressant drugs have been suggested to permit better long-term transplant outcomes and a decrease in incidence of gingival overgrowth. The aim of the present paper is to summarize current knowledge regarding aetiology, pathogenesis and management of gingival overgrowth induced by Cyclosporine A.
Abstract: Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the ano-genital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36) -risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-beta2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed. Major aims of this review are to update the understanding of HPV activities with respect to oral oncology and to comment on the HPV DNA reported frequencies in OSCC and potentially malignant oral lesions. A computer database search was performed, through the use of MEDLINE (PubMED) and Cochrane Library, for the last three decades. Search key words used were: human papillomavirus, HPV and cancer, HPV and oral lesions, HPV and oral premalignant lesions, HPV and oral cancer, HPV and HNSCC, HPV and oral mucosa. The search was of all fields, all languages and all dates available.
Abstract: BACKGROUND: Cutaneous CD30+ lymphoproliferative disorders (LPDs) are a spectrum of disease associated with a favourable prognosis. Systemic anaplastic large cell lymphoma (ALCL), although morphologically and phenotypically similar, differs in clinical presentation and has a less favourable biological behaviour. Dysregulation of apoptosis, the process regulating cell population by programmed death, can explain the differences among these disorders. OBJECTIVES: We investigated the expression of two inhibitors of apoptosis, survivin and Bcl-2 protein, in serial skin lesion samples from CD30+ LPDs compared with systemic ALCL. METHODS: Immunohistochemical analysis with antibodies against anaplastic lymphoma kinase (ALK)-1 protein, survivin and Bcl-2 protein was performed in 10 cutaneous CD30+ LPDs (five lymphomatoid papulosis, five ALCL) and 18 systemic ALCLs. Reverse transcription-polymerase chain reaction studies for ALK and ALK/nucleophosmin were also performed. RESULTS: Cutaneous CD30+ LPDs shared a heterogeneous expression of cytoplasmic survivin with all systemic ALCLs, and of Bcl-2 with systemic ALK- ALCLs; however, they differ from systemic ALK- ALCLs because they lack nuclear survivin (P = 0.045), and from systemic ALK+ ALCLs by a higher expression of Bcl-2 (P = 0.045) and a lack of ALK-1. Overall, coexpression of Bcl-2 and nuclear survivin in CD30+ LPDs was associated with a less favourable disease survival. CONCLUSIONS: The different patterns of expression of Bcl-2 and survivin in CD30+ LPDs might have an impact on their different biological and clinical behaviour. Moreover, nuclear localization of survivin, similarly to ALK, may be a useful marker for predicting a systemic form of ALCL with cutaneous presentation.
Abstract: Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterised by abnormal clavicles, patent sutures and fontanelles, supernumerary teeth, short stature, and a variety of other skeletal changes. The disease gene is CBFA1/RUNX2, which is mapped to chromosome 6p21. Inactivation of the CBFA1/RUNX2 gene by mutations is involved in the skeletal defects that occur in patients with CCD. CBFA1/RUNX2 controls the differentiation of precursor cells into osteoblasts and is essential for membranous as well as endochondral bone formation. In this study of a 14-yr-old boy with typical CCD phenotype, the authors found a novel CBFA1/RUNX2 gene mutation. All of the amplified segments from the patient's CBFA1/RUNX2 gene were identical to those obtained in controls, except for the one spanning the exon 7 and intron/exon boundary regions. Direct sequencing of the PCR product showed a heterozygous T-to-A transition mutation at nucleotide 1182 in exon 7, leading to Y394X mutation. The predicted protein product lacks 128 amino acids, including part of the PST domain. Identification of this novel mutation constitutes a further step in elucidating the pathogenesis of this autosomal disorder.
Abstract: Human telomerase reverse transcriptase (hTERT) gene expression in resected specimens of oral squamous cell carcinoma (OSCC) and their surrounding tissue, either apparently normal or clearly histologically dysplastic, was evaluated by both real-time RT-PCR and immunohisto-chemical protein analyses. The expression level of hTERT in oral dysplasia and in OSCC was markedly higher than in normal tissues. The correlation between hTERT expression in OSCC and clinico-pathological parameters or survival of OSCC patients was statistically analyzed. Our study demonstrates that there is no significant relationship between hTERT expression and classical clinico-pathological parameters. Interestingly, survival analysis showed both overexpressing cases and lower survival rate in the early stage of OSCC (p=0.03 for immunohistochemistry; p=0.04 for RT real-time PCR). The histological location of hTERT in these tumors has been discussed in the context of the cancer stem cell theory.
Abstract: The incidence of eating disorders has progressively increased over the last several years, mainly affecting both the health and quality of life of young women. Such disorders are primarily an outlet for manifest psychic suffering and secondarily, they jeopardize the integrity and function of multiple organ systems resulting in significant morbidity and sometimes, life-threatening outcomes. The complex emerging interplay of etiopathogenetic factors poses many challenges in their prevention and management, which is further complicated by a reluctance by patients with eating disorders to seek medical evaluation and treatment. Recognition of the oral manifestations is important because these signs and symptoms can provide insights about disease progression and parallel general health and psychic status. Oral health care providers may be one of the few providers contacted by this patient population seeking recall prophylaxis or urgent dental care. Thus, improving understanding and knowledge of both general medical aspects of eating disorders and their oral manifestations could be of great impact in elevating the attention of health providers towards this group of very debilitating disorders and, consequently, improving their overall prognosis. In this paper we will review and discuss all these aspects.
Abstract: BACKGROUND: Osteonecrosis of the jaw is a well known potential complication of bisphosphonate treatment but its pathogenesis is poorly understood. The current management of patients with bisphosphonate-associated osteonecrosis (BON) is based on "expert recommendations" and there is a recognized need of better evidence. We report two cases where BON hid jaw metastases and use them to discuss some limitations of the current recommendations. PATIENTS: Two patients undergoing long-term I.V. amino-bisphosphonate treatment for metastatic cancer presented with areas of intraorally exposed jawbone. Bisphosphonate-associated osteonecrosis was diagnosed on the basis of medical history, clinical and radiological features. They underwent surgical resection of the affected jaw due to unrelenting pain and lack of response to conservative treatments. RESULTS: Histological examination of the surgical specimen revealed cancer cells at the margins of the site of osteonecrosis. Our patients did not undergo bone biopsy according to current recommendations, due to lack of clinical and radiological signs suggestive of jaw metastases. CONCLUSIONS: Our findings show that: i) patients with BON may also have jaw metastases; ii) there may not be clinical or imaging hints to this fact and; iii) that a biopsy based on careful selection of the site (with inclusion of necrotic margins) may be needed to reach the correct diagnosis. Further studies should be performed on this topic because of its very important prognostic implications.
Abstract: Recently, jawbone osteonecrosis has been largely reported as a potential adverse effect of bisphosphonate (BP) administration. Because of the peculiar pharmacokinetic and pharmacodynamic features of the BF (mainly for i.v. administration), their efficacy and large use, some major issues have to be taken into account extendedly both by oncologists and by dentists: 1) therapeutic dental protocol for patients with diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ); 2) dental strategies for patients in former or current i.v. BF treatment and in absence of BRONJ signs; 3) strategies for patients before i.v. BF treatment. Clinical features and guidelines for the management of this condition have been investigated and reported, sometimes with unclear indications; hence, on the basis of the literature and our clinical experience, major end points of this paper are providing our run protocols for the issues above described and, finally, focusing on a crucial, but not extensively investigated point: the early and correct diagnosis of BRONJ versus metastatic jaw lesions in cancer patients.
Abstract: BACKGROUND: P63 is the protein codified by p63 gene, a p53 gene homolog, known for its pivotal role in cell cycle regulation, and involved in the tumor differentiation. Aims of the present study were to assess the frequency and pattern of p63 protein expression in oral squamous cell carcinoma (OSCC) in relation to the main tumour characteristics and to verify whether p63 can be considered a marker of prognosis in patients with OSCC. MATERIAL AND METHODS: In a retrospective study, a cohort of 64 OSCC patients was investigated for p63 protein expression and its cellular localization by immunohistochemistry (monoclonal mouse anti-human p63 protein-clone 4A4). After grouping by p63 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. RESULTS: The overall frequency of p63 overexpressed was of 57.8 percent. Various p63 staining patterns were observed according to G score, with a significant correlation between p63 overexpression and the lowest G score (P < 0.0001). No statistically significant difference was found between p63 pattern expression and age, sex, staging. OSCC patients with p63 overexpressed were found to have a poorer survival rate with respect to OSCCs with a normal pattern of expression (P = 0.024). CONCLUSIONS: On the basis of these results, it is possible to suggest p63 pattern expression as a reliable indicator of histological grading and an early marker of poor prognosis.
Abstract: BACKGROUND: Many coeliac disease patients with atypical symptoms remain undiagnosed. AIM: To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis. PATIENTS AND METHODS: One hundred and ninety-seven coeliac disease patients and 413 controls were recruited and the oral examination was performed. RESULTS: Forty-six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten-free diet. Multi-logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427-4.926) and soft tissue lesions (OR = 41.667, CI = 18.868-90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis. CONCLUSIONS: The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive-predictive value of these lesions for coeliac disease diagnosis was low.
Abstract: We investigated expression levels of Nicotinamide N-Methyltransferase (NNMT), an enzyme involved in the biotransformation of many drugs and xenobiotic compounds, in oral squamous cell carcinoma (OSCC). Measurements were performed by semi-quantitative RT-PCR and quantitative real-time PCR in tumor and matched adjacent healthy tissue. Interestingly, NNMT was up-regulated in most of the favorable OSCCs, while no marked NNMT expression alterations between tumor and normal mucosa were detected in most of the unfavorable OSCCs. Western blot and immunohistochemical analyses also were performed and the relationship between tumor characteristics and NNMT levels in OSCC were studied to evaluate the effectiveness of NNMT as a prognostic marker in the squamous cell carcinoma of the oral cavity. In summary, the present study suggests that NNMT may have potential as a biomarker and a therapeutic target for OSCC.
Abstract: This study describes, microscopically, the pathologic findings correlated to malpositioning of the human temporomandibular joint disc. The specimens studied consisted of 21 discs removed from patients affected by temporomandibular joint arthropathy. The specimens were cut longitudinally and were fixed overnight in 10% neutral-buffered formalin. They were embedded in paraffin with anatomic orientation preserved. Three- to 4-microm thick sections were cut according to routine procedures and mounted on slides. Then they were stained with Goldner-modified-Mallory staining used for morphologic study at light microscopy. Abnormal collagen fiber arrangements, fragmentation of collagen fibrils, new vessel formation, meniscal tears, mucoid degeneration of the disc matrix, chondrocyte-like cells proliferation, sometimes with clonal aggregation, and hyalinization were detected in temporomandibular joint disc specimens with internal derangement, although with a different extent. From our observations, it seems that in most cases, the temporomandibular joint disc responded to internal derangement without reduction with a fragmentation of collagen fibers because hyalinization of disc matrix occurred very rarely. Moreover, disc derangement without reduction is characterized also by a change in cell population phenotype.
Abstract: BACKGROUND: Mammary tumors are a very common neoplasm in the dog and show histological features and biological behaviour similar to human mammary carcinomas. Recently, a pathway named Wnt-1, involving beta-catenin and APC protein, has emerged as an important player in many human tumor types, including mammary neoplasms. MATERIALS AND METHODS: Thirty-five samples of canine mammary tumors (10 benign and 25 malignant) were studied in order to evaluate the co-expression of beta-catenin, APC protein and E cadherin with confocal laser microscopical observation, by western blot analysis and by correlating data obtained with the histological grade of tumours. RESULTS: A progressive decrease of E-cadherin together with disruption of beta-catenin expression was observed in less differentiated malignant tumors. In addition, a loss of beta-catenin membranous distribution and a cytoplasmic accumulation was often coexpressed with disrupted expression of APC protein. Western blot analysis showed a progressive increase of beta-catenin in malignant tumors, which could be the expression of disrupted /-catenin catabolism leading to cytoplasmic accumulation. In some less differentiated malignant tumors, a marked beta-catenin decrease was also observed. This feature could be linked to mutations in beta-catenin gene coding for a truncated and lighter protein. CONCLUSION: These results may indicate the multifunctional role played by beta-catenin in canine mammary oncogenesis.
Abstract: Discoid Lupus Erythematosus (DLE) is a chronic disease with a typical cutaneous involvement. This pathology rarely involves mucosa: oral cavity is interested in 20 percent of DLE patients. We describe a case of oral DLE in a 50-year-old woman with an anamnesis for autoimmune disorders. This study shows the helpful role of immunofluorescence in the diagnosis of autoimmune diseases. The first diagnostic step was the clinical observation of the oral mucosa: the lesion area was erythematous, atrophic and hyperkeratotic. The patient then underwent laboratory examination. We utilized human epithelial cells (Hep-2010) for Indirect Immuno-Fluorescence (IIF). Moreover, the biopsy site for Direct Immuno-Fluorescence (DIF) and histopathological analysis was the untreated oral lesion. IIF detected an increase of Anti-Nuclear Antibody (ANA) and positivity for SSA-RO. By DIF, we observed IgG/IgA/fibrinogen along basal layer. Multiple biopsies reported signs of chronic basal damage. Steroid systemic therapy induced a considerable lesion regression. We suggest the use of immunofluorescence with the integration of further data to improve diagnosis of rare diseases and to establish a suitable therapy.
Abstract: Classification and prognosis of larynx squamous cell carcinoma (LSCC) depends on clinical and histopathological examination. Currently, expression profiling harbors the potential to investigate, classify, and better manage cancer. Gene expression profiles of 22 primary LSCCs were analyzed by microarrays containing 19,200 cDNAs. GOAL functionally classified differentially expressed genes, and a novel "in silico" procedure identified physical gene clusters differentially transcribed. A signature of 158 genes differentiated tumors with nodal metastasis. A novel statistical method allowed categorization of metastatic tumors into 2 distinct subgroups of differential gene expression patterns. Among genes correlated to nodal metastatic progression, we verified in vitro that NM23-H3 reduced cell motility and TRIM8 were a growth suppressor. Six chromosomal regions were specifically downregulated in metastatic tumors. This large-scale gene expression analysis in LSCC provides information on changes in genomic activity associated with lymphonodal metastasis and identifies molecules that might prove useful as novel therapeutic targets.
Abstract: Squamous cell carcinoma (SCC) is one of the most common malignant cancer of the oral cavity encompassing at least 92.8% of all oral malignancies. Despite improved diagnostic and therapeutic methods over the 20 last years, this tumour is still characterized by a high rate of mortality. The latest advances of molecular biological methods have contributed to better understand the mechanisms involved in the oral carcinogenetic process. Deregulation of cell cycle, apoptosis and cell-cell/cell-matrix adhesions are considered the pathways mainly influencing this multistage event and scientific researches over the last decade have been performed in order to investigate the biological diagnostic and prognostic parameters related to these events (i.e. tumour growth markers, markers of tumour suppression and anti-tumour response, angiogenesis markers, markers of tumour invasion and metastatic potential, cell surface markers, intracellular markers, markers derived from arachidonic acid, and enzymatic markers). The aim of the present review was to outline the current knowledge on the role of some of these tumour biological markers in carcinogenesis of oral SCC.
Abstract: BACKGROUND: Solitary fibrous tumor (SFT) is an uncommon but well-characterized soft tissue tumor that was first described as a pleural lesion and now is considered ubiquitous, having been detected at many extra-pleural sites (abdominal cavity, orbit, upper respiratory tract, and oral cavity). Histologically, SFT may show wide morphological variability of both its cellular and stromal components, which may lead to incorrect diagnosis especially when dealing with small incisional biopsies. MATERIALS: We report on the clinical, morphological and immunohistochemical features of eight SFT occurring in the oral cavity. RESULTS: Microscopically all eight tumors showed widely variable morphological features in terms of cellular density and stromal architecture, thus simulating benign fibrous histiocytoma, schwannoma, hemangiopericytoma or low-grade sarcoma in distinct areas of the same lesion. Among these eight cases, five had been diagnosed as SFT, two as benign fibrous histiocytoma and one as low-grade sarcoma. CONCLUSIONS: In consideration of the heterogeneous morphological appearance of SFT, inaccurate sampling of the mass may lead to misdiagnosis and inappropriate treatment. Therefore, an accurate histological examination of multiple tissue sections is advised, along with the use of appropriate immunostains.
Abstract: COX-2 expression in tumour cells has been associated with carcinogenesis in many human neoplasms, including head and neck cancer, while the COX-1 isoform of the cyclooxygenase enzyme is constitutively expressed in normal tissues. We measured COX-1 and COX-2 m-RNA expression in samples of both oral cancer and matched oral mucosa from 22 patients by RealTime RT-PCR; clinic pathological data (grading, TNM staging, inflammation, follow-up) of all patients were available for statistical evaluation. Most of the tumor samples in our study expressed at least one cyclooxygenase enzyme (COX-1 or COX-2 mRNA) more than their matched normal oral mucosa (p<0.05), with no correlation with the entity of inflammation, and a significant inverse relationship was found between COX-1 and COX-2 in each sample. Higher levels of COX-2 expression were associated with poor disease-free survival (p<0.05), but not with overall survival and higher tumor stage and grade. Our results suggest that COX-1 may play a role in oral carcinogenesis, and could be regarded as a potential therapeutic target by chemo preventive drugs; moreover, COX-2 expression might be addressed as a new prognostic tool in the clinical management of OSCC.
Abstract: Survivin is a recently described inhibitor of apoptosis and mitotic regulator which is selectively over-expressed in human tumors. Its expression rate is predictive of disease progression, early recurrences and resistance to therapy. Up-regulation of survivin in oral pre-malignant lesions (OPL) and in oral squamous cell carcinoma (OSCC) has already been demonstrated in previous studies. A critical step for activation of survivin has been identified in the phosphorylation on Thr34 by the main mitotic kinase p34cdc2-cyclin B1. The aim of this work was to investigate the relationship between survivin, its phosphorylated active form (p-survivin) and M-phase promoting factor (MPF), p34cdc2-cyclin B1 in oral carcinogenesis. 32 OSCCs and 17 OPLs from surgical specimens were studied for cyclin B1, p-survivin, survivin, and p34cdc2 expression by immunohistochemistry. All cases of OSCC expressed survivin and its expression rate was correlated to p-survivin levels (P<0.05). Cyclin B1 was positive in 80% of cases, while p-34cdc2 was over-expressed in all OSCCs. All OPLs associated with OSCC expressed survivin and its levels were correlated to p-survivin levels (P<0.05). Cyclin B1 was positive in 70% of cases, while p-34cdc2 was positive in all OPLs. In conclusion, this study demonstrated that MPF, survivin and p-survivin are expressed during early and late phase of oral carcinogenesis. MPF proteins, which are co-expressed on mitotic apparatus, could represent a potential target for therapies based on manipulation of survivin phosphorylation, which would induce apoptosis in cancer cells.
Abstract: Cells with a dendritic morphology and/or expression of dendritic cell (DC) markers have been repeatedly described in several human tumors, but the distribution and density of melanoma-associated DCs have not yet been reported. The aim of the present study is to analyze the density and topographical distribution of melanoma-associated DCs and their relation with CD3(+), CD4(+) and CD8(+) T lymphocytes in forty cases of cutaneous human melanoma. In melanocytic tumours different pools of DCs were recognised in the epidermis and in the dermis, particularly in intimate relation with lymphocyte clusters inside the melanocytic proliferation, and more often at the edges of tumours. The number of Langerin-positive DCs showed an inverse correlation with tumour depth (correlation coefficient r= -0.59, P=0.0001) and was significantly lower in thick melanomas compared to thin and intermediate ones (P<0.0005). The density of CD83(+) DCs was significantly lower in thick melanomas compared to thin and intermediate ones (P<0.009). A significant correlation was found between the density of the two DCs subsets (r=0.57, p<0.0001). The number of CD3(+) lymphocytes was inversely correlated to the depth of infiltration (r=-0.596, P<0.0001): melanoma cases with II-III Clark level showed a higher T lymphocyte mean density compared to cases with IV-V Clark level (P<0.0001). T lymphocyte density was significantly lower in thick melanomas compared to thin and intermediate melanomas (P<0.0005). In conclusion, our study indicates a progressive loss of DCs and T lymphocytes in the neoplastic progression of melanomas; further identification of the molecular pathways involved in the functional impairment of these immunitary cells may lead to new immunotherapeutic approaches for melanoma patients that would improve the clinical outcome of the patients.
Abstract: The present paper reviews relationship between chronic periodontitis and cardiovascular diseases. Original papers on this subject, published in English in the period between 2001 and the first semester 2006, were located in the MEDLINE/PubMed database. Additional studies were obtained by searching reference lists of previously published papers. Periodontal infection provides a chronic reservoir of inflammatory mediators and cytokines, lipopolysaccharide, which contribute to the formation of atheroma. Moreover, periodontal pathogens can penetrate the epithelial barrier of the periodontal tissues and reach the blood stream, carrying out a local atherogenic activity. Some studies indicated that periodontal treatment could result in reduction of cardiovascular events. If these results are confirmed in further intervention studies, the prevention and the treatment of periodontitis should be considered as factors able to avoid or reduced the onset and/or evolution of cardiovascular diseases.
Abstract: In oral squamous cell carcinomas of the head and neck, Laminin-5 gamma2 has been associated with tissue invasion, lymph node metastasis and histopathological grading. In the present study, we compared the expression of the subunit gamma2 of Laminin-5 under normal, dysplastic and invading epithelia in 65 biopsies previously diagnosed for oral squamous cell carcinoma. The number of gamma2-positive cells were analyzed in relation to patients' survival, tumor grading, size of the lesion, TNM stage, histopathological pattern of invasion and inflammatory reaction. Biopsies of oral squamous cell carcinomas were deparaffinised, processed for antigen unmasking procedures and stained with antibody anti-Laminin-5 gamma2. By light microscopy, 4 optical fields of x200 were selected in three different areas including normal, dysplastic and invading epithelia. Positive cells were counted and divided into three categories, which included <20 cells, between 21 and 50 cells and >50 stained cells. Patient survival was analyzed by Kaplan-Mayer curves. gamma2-positive cells were found in the basal layer of dysplastic epithelium, within inflammatory infiltrate, at the margins of differentiated invading islands and at the forefront of undifferentiated invading nests. Observations showed that an increased number of gamma2-positive cells correlated significantly with a shorter life expectancy under invading epithelia (log-rank test p<0.05), not when a count was performed under normal or dysplastic epithelia of the same patient. The number of gamma2-positive cells also correlated with the histopathological pattern of invasion. Our results show that gamma2 may be a reliable prognostic tool for oral squamous cell carcinomas.
Abstract: Dysphagia, defined as a difficulty in swallowing of fluids and/or food, is one of the most frequent symptoms of oesophageal, gastrointestinal or ENT diseases. Interestingly, dysphagia can be also the initial or late symptom of several oral diseases: e.g. traumatic ulcerations, immunomediated or infectious lesions, malignant neoplastic disease or mucositis in chemio-radiotherapy. The presence of this frequent symptom, with or without oral evident lesions, can suggest the presence of oral or perioral diseases, promoving adequate diagnostic-therapeutic management. In this paper, authors describe aetiology, pathogenesis and clinical aspects of oral diseases, as being more frequently associated with dysphagia; moreover, they describe the most important clinical and epidemiological features of systemic diseases associated with dysphagia.
Abstract: The possibility of the non-parenteral Hepatitis C Virus (HCV) transmission is supported by the demonstration that the actual virus is present in several body fluids, including saliva. From a review of the literature many investigators have found the presence of HCV-RNA in saliva, however, widely contrasting results emerge, with detection rates ranging from 0-100%. To further examine HCV salivary shedding, saliva samples were collected from 46 chronically HCV-infected patients and tested for HCV-RNA and occult blood. Quantification and genotyping of serum HCV-RNA were also carried out for each patient. HCV-RNA was detected in 39.13% of the saliva samples. The viral salivary shedding was significantly related to viraemia levels, serum viral genotype and the presence of salivary occult blood. Our findings indicate that the HCV salivary shedding occurs in about one third of HCV infected patients, but seem to suggest that it is unlikely when the serum viral genotype is 3a. Moreover, blood leakage into the oral cavity is possibly the main source of the salivary HCV-RNA. Although the occurrence of the viral salivary shedding does not necessarily mean that HCV transmission occurs by saliva, our results suggest the need for further investigations into the biological factors possibly involved in HCV mucosal transmission related to both the source and the exposed subjects.
Abstract: We aimed to evaluate if in oral squamous cell carcinoma (OSCC) there is a relationship between histological grading (HG), TNM clinical stage and HPV infection; and to study the performance of fuzzy logic compared to traditional statistics, in the analysis of HPV status and correlates of OSCC. In cross-sectional analysis, the study group comprised 63 patients (mean age 68.89 years (SD +/-11.78), range (32-93); males 28 (44.4%), females 35 (55.6%)) with OSCC histologically diagnosed. HPV-DNA was studied in exfoliated oral epithelial cells by nested PCR (MY09/MY11 and GP5+/GP6+ primers). Data were analysed in parallel by traditional statistics with multivariate analysis and a fuzzy logic (FL) technique (membership functions as input, the ANFIS methodology, and the Sugeno's model of first order). HPV infection was detected in 24/63 (38.1%) of OSCC, as being HPV+ve 14/36 (38.9%) in G1, 7/18 (38.9%) in G2, and 3/9 (33.3%) in G3; HPV+ve 8/33 (24.2%) in Stage I, 9/12 (75.0%) in Stage II, 6/11(54.5%) in Stage III, and 1/7 (14.3%) in Stage IV. In both methods of analysis, no significantly increased risk of HPV infection was found for any HG score; whereas, TNM stage II was significantly associated to HPV infection (p=0.004; OR=9.375 (95% CI=2.030:43.30); OR'=11.148 (95% CI=1.951:43.30)), and, in particular, to primary tumour size T2 (p=0.0036; OR=7.812 (95% CI=1.914:31.890); OR'=9.414 (95% CI=1.846:48.013)); FL (% of prevision: 79.8; Root Mean-Square Error (RMSE): 0.29). No association was found between HPV infection and any demographical variable. Our findings show an association between HPV infection with TNM (stage II-T2), but not with histological grading of OSCC. Also, FL seems to be an additional effective tool in analysing the relationship of HPV infection with correlates of OSCC.
Abstract: AIM: Coeliac disease is characterized by oral manifestations, such as dental enamel defects and recurrent oral aphthae. In this study we compared the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) between patients diagnosed with coeliac disease and healthy controls. METHODS: A total of 72 patients with coeliac disease were studied together with 162 normal healthy subjects as controls to individualize the prevalence of enamel defects and recurrent aphthous stomatitis (RAS) in this disease. RESULTS: Dental enamel defects were found in 14/70 (20%) coeliac patients and in 9/159 (5.6%) controls. In particular, 13/53 (24.5%) coeliac patients with mixed or permanent dentition and 1/17 (5.8%) coeliac children with deciduous dentition had enamel defects. Altogether, 9/145 (6.2%) control subjects with mixed or permanent dentition had dental enamel defects. None of the controls with deciduous dentition had enamel defects. Thus, the enamel defects occurred more frequently in coeliac patients (p < 0.001). Regarding RAS, 24/72 (33.3%) coeliac patients and 38/162 (23.4%) control subjects had aphthous ulcers. Statistically significant differences were not observed between the two groups (p > 0.05). One in three coeliac subjects suffering from RAS received benefit from a gluten-free diet. CONCLUSION: In the present study, the prevalence of enamel defects was found to be greater in coeliac patients than healthy controls. Even though the prevalence of RAS in coeliac subjects varied from healthy controls, the difference was not statistically significant. However, more than 1/3 coeliac subjects suffering from RAS benefited from a gluten-free diet.
Abstract: Since Raloxifene, a drug used in osteoporosis therapy, inhibits the osteoclast functions but not osteoblast functions, it could improve the recovery during implant surgery. This preliminary report describes a simple method to link, through a covalent bond, Raloxifene to titanium by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by the IR-FT and SEM. To evaluate the biological response of osteoblast-like cells to this implant, we compared expression gene profiling of cell cultures on Raloxifene conjugated implant and normal implant by DNA microarray. By using DNA microarrays containing 19,200 genes, we identified differently expressed genes in osteoblast-like cell line (MG-63). Surface Raloxifene conjugated implants have been shown to have a relevant importance in modifying cell response. This result could be an interesting starting point for the use of an immediate functional loading of implants.
Abstract: BACKGROUND: The purpose of this study was to investigate in oral breathing children the qualitative and quantitative effects on aerobic and facultatively anaerobic oropharyngeal microflora of respiratory function improved by rapid palatal expansion (RPE). METHODS: In an open clinical trial, we studied 50 oral breathers, aged 8 to 14 years and suffering from both maxillary constriction and posterior cross-bite. At baseline, patients were examined by a single otorhinolaryngologist (ENT), confirming nasal obstruction in all subjects by posterior rhino-manometric test. Patients were evaluated three times by oropharyngeal swabs:1) at baseline (T = 0); 2) after palatal spreading out (T = 1); and 3) at the end of RPE treatment (T = 2). With regard to the microbiological aspect, the most common and potentially pathogenic oral microrganisms (i.e. Streptococcus pyogenes, Diplococcus pneumoniae, Staphylococcus aureus, Haemophilus spp, Branhamella catarrhalis, Klebsiella pneumoniae, Candida albicans) were specifically detected in proper culture plates, isolated colonies were identified by means of biochemical tests and counted by calibrated loop. The data were analyzed by means of the following tests: Chi-square test, Fisher's exact test and Wilcoxon's test. RESULTS: After the use of RME there was a statistically significant decrease of Staphylococcus aureus stock at CFU/mLat T1(P = 0.0005; Z = -3,455 by Wilcoxon Rank test) and T2 (P < 0.0001; Z = -4,512 by Wilcoxon Rank test) vs T0. No significant changes were found for the other examined microrganisms. CONCLUSION: Our data suggest that RPE therapy in oral breathers may strongly reduce the pathogenic aerobic and facultatively anaerobic microflora in the oral pharynx after a normalization of the upper airways function, and may reduce the risk of respiratory infections.
Abstract: We report the clinical, radiographic and histological features of 15 paradental cysts of the first and second molars and recommend conservative surgical treatment. Twelve young patients were operated on for 15 paradental cysts of the first and second molars, and had conservative operations with partial preservation of the mandibular cortical bone. After 2 years there had been no recurrences. The differential diagnosis of paradental cyst was fundamental to allow the correct treatment and the early diagnosis of lesions on the opposite side. The maintenance of periodontal hygiene in the immediate and late postoperative periods was an aid to ensure complete remission of the lesions.
Abstract: The proto-oncogene c-Met has been suggested to be associated with progression of squamous cell carcinoma of the head and neck. The aims of the present study were to assess the prevalence of c-Met expression in oral squamous cell carcinoma (OSCC) and to verify whether c-Met can be considered a marker of prognosis in these patients. In a retrospective study, a cohort of 84 OSCC patients was investigated for c-Met expression and its cellular localization by immunohistochemistry. After grouping for c-Met expression, OSCC patients were statistically analyzed for the variables age, gender, histological grading, tumor node metastasis, staging and overall survival rate. Univariate and multivariate statistics were used for data analysis. Sixty-nine cases (82.2%) of OSCC showed immunopositivity, with a mainly membranous expression and scattered areas also showing a cytoplasmic localization, whereas 15 cases (17.8%) did not show c-Met. No statistical association was found between c-Met expression and any variables considered at baseline, apart from the higher number of c-Met positivity in females (p = 0.026). Among positive tumors, well-differentiated areas showed low or absent cytoplasmic expression, while low-differentiated areas showed both membranous and cytoplasmic positivity. In terms of prognostic significance, c-Met expression was found to have an independent association with a poorer overall survival rate (p = 0.036). On the basis of these results, it is possible to suggest c-Met as an early marker of poor prognosis, a hallmark of aggressive biological behavior in OSCC, suggested to be useful in identifying cases of OSCC before the relapse.
Abstract: INTRODUCTION: Adequate brushing of oral mucosa is important for accurate human papillomavirus (HPV) detection in potentially malignant (oral leukoplakia [OL], oral lichen planus [OLP]) and malignant (oral squamous cell carcinoma [OSCC]) lesions. Since various factors may limit the adequacy of oral brushing and, consequently, the accuracy of HPV detection, modified sampling procedures should be evaluated for their effect on HPV frequency and/or types detected. AIM: To compare the HPV frequency in samples obtained by brushing the lesion site with the frequency in samples obtained by brushing an apparently normal adjacent site. The correlation between HPV frequency and keratinization of the site affected by the lesion, as well as sociodemographic variables (age, sex, smoking and drinking habits), was also examined. METHODS: HPV DNA was detected in brushing samples from 50 patients with OL, 49 with OLP, and 17 with OSCC. Polymerase chain reaction (PCR) amplification was performed by MY09/MY11 and GP05+/GP06+ primers; the HPV type was identified by DNA sequencing and a reverse hybridization (line probe) assay. Data were analyzed by the Z test, the Fisher's exact test, the chi-square test, odds ratio (OR), and a logistic regression model. RESULTS: HPV DNA was detected in 22% of samples from lesion sites and in 16% of samples from adjacent sites (p = 0.22) in patients with OL, in 24.5% and 22.4% of samples from lesion and adjacent sites, respectively, in patients with OLP (p = 0.40), and in 35.3% and 41.2% of samples from lesion and adjacent sites, respectively, in patients with OSCC (p = 0.36). Lesions adjacent to HPV-positive normal sites had an increased rate of HPV detection (OR = 30; 95% CI 9.57, 94.1). HPV-18 was the most frequent genotype, followed by HPV-6, -16, -33, and -53. HPV prevalence was reduced in lesions at keratinized sites (14.5%) compared with non-keratinized sites (34.4%; p = 0.007; OR = 0.32; 95% CI 0.13, 0.81). DISCUSSION: In patients with OL, OLP, or OSCC, a high prevalence of HPV infection was shown in apparently normal sites adjacent to lesion sites infected by HPV. The lower HPV frequency in lesions at keratinized sites suggests that HPV detection by lesion brushing is affected by keratinization. The keratinized epithelium may be less susceptible to HPV infection or, alternatively, the highly proliferative activity in non-keratinized sites may predispose to HPV infection. CONCLUSION: Results from this study indicate that taking samples from normal sites adjacent to oral lesions may be of value in HPV detection, particularly when the lesions are located at keratinized sites. This sampling procedure may allow more accurate diagnosis of HPV infection compared with sampling only the lesion site, and may also represent a reliable method to investigate the biological characteristics of HPV infection and related oral carcinogenesis.
Abstract: BACKGROUND: The aims of the present study were to assess the prevalence of HSP27 expression in oral squamous cell carcinoma (OSCC) and to verify whether HSP27 can be considered to be a marker of prognosis in patients with OSCC. MATERIALS AND METHODS: The immunohistochemical expression of HSP27 was evaluated in 57 OSCC, who received standard treatment and monitoring. After grouping for HSP27 expression, OSCCs were statistically analysed for the variables age, gender, histological grading, TNM, staging and survival rate. Univariate and multivariate analyses were performed. RESULTS: HSP27 was found to be reduced in 31 OSCC and was normally expressed in 26 OSCC. The pattern and intensity of HSP27 immunolabelling did not show significant differences in relation to any variables retrospectively considered. In terms of prognostic significance, HSP27 reduced expression was found to have an independent association with the poorest overall survival rate (p=0.009; OR= 4.404; CI=1.444:13.427 by Cox regression). CONCLUSION: HSP27 reduced expression is an early marker of poor prognosis, useful in identifying aggressive biological behaviour in OSCC cases even before relapse.
Abstract: We investigated mRNA expression of the genes involved in the apoptotic mechanism in oral squamous cell carcinoma (OSCC) by cDNA microarray. The aim of this study was to identify genes mainly involved in tumorigenesis, comparing the difference of gene expression in neoplastic and non-neoplastic tissues. Eight frozen samples of OSCC and the corresponding normal oral mucosa were treated to obtain mRNA. The mRNA extracted from these specimens was converted into cDNA and analyzed with SuperArray GEArray Q Series Human Apoptosis Gene Array kit. Our results showed that in OSCC there is a different expression of CRADD, FADD, ATM and APAF-1 genes compared to normal mucosa. Real-Time PCR, and Western blot analysis were performed on a separate cohort of patients in order to confirm the results obtained by DNA microarray. Our analysis of apoptotic process through microarray technology confirmed that different molecules could be responsible or favour the imbalance of apoptosis in cancer tissues. Microarray technology has made it possible to analyze the expression of multiple genes in a single experiment. However, most commercial array kits, designed to include as many genes as possible, produce a vast amount of data that often is difficult to interpret. In addition, the cost of equipment is often prohibitive. In contrast, the focused kit used was a complete, affordable and effective method to improve knowledge of molecular specific pathways.
Abstract: In head and neck district, major salivary gland diseases seem to have a considerable epidemiological and clinical impact, especially in obstructive disease. Major salivary glands, in fact, having a ductal system can develop several diseases: sialoadenitis, sialodochitis and sialoceles. Particularly, the obstructive sialoadenitis, with or without sialolithiasis, are the most frequent inflammatory disorder, especially for submandibular gland. In the clinical practice, the diagnostic approach for obstructive sialoadenitis up to now consisted of traditional Rx, ultrasonographic technique, scintigraphy technique, C.T., sialography technique with contrast or sialography M.R. Since '90 years, lithotripsy and, later, sialendoscopy have been introduced as gold standard diagnostic procedures in case of obstructive sialoadenitis and also as therapeutic tool when possible. In this way, it has been possible to offer a valid alternative in place of traditional surgical techniques, with a less invasive and more efficacious approach.
Abstract: This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.
Abstract: Psoriasis is a chronic skin disease, characterized by epidermal hyperplasia, inflammation, angiogenesis and vascular remodelling. An immunohistochemical study on fifteen cryosections of psoriatic skin was performed using antibodies against VEGF, HIF1-alpha, CD34, Factor VIII, MMP-2, MMP-9, TIMP-1 and TIMP-2. Psoriatic skin showed a diffuse VEGF positive staining (13.15+/-6.6), while no expression was observed in normal epidermis. No or faint HIF-1alpha immunostaining was detected in healthy skin, while in psoriatic skin HIF-1alpha was diffusely expressed. A positive correlation between HIF-1alpha and VEGF was reported in psoriatic skin (r= 0.644; p=0.010). In psoriatic sections CD34 expression was significantly higher in respect to control skin (19.15+/-12.61 vs 3.0+/-0.23; p= 0.04), factor VIII immunostaining also demonstrated a significant increased development of the microvasculature in comparison with healthy skin (18.39+/-8.16 vs 7.4+/-0.20; p= 0.033). Total MMP-2 expression of healthy skin (30+/-2.26) was significantly lower in respect to the MMP-2 psoriatic skin (71.5+/-4.13; p= 0.0001) and a positive correlation was observed between VEGF and MMP-2 in psoriatic patients (r= 0.688; p= 0.046). In psoriatic skin MMP-9 expression was significantly increased in comparison to control skin (31+/-3.3 vs 8+/-6.1; p=0.007). All cases of psoriatic skin tissue showed that TIMP-2 and TIMP-1 expression statistically decreased in psoriatic skin (respectively 11+/-1.2 and 12+/-1.5) in comparison with healthy skin (respectively 15+/-3.2 and 53+/-3.8; p=0.0001). In conclusion, we observed that VEGF overexpression correlated with HIF-1alpha and MMP-2 expression, underlining the role of VEGF in psoriasis as a key factor in the link between inflammation and angiogenesis.
Abstract: p63 belongs to a protein family that includes 2 structurally related proteins, p53 and p73. The aim of this study was to investigate the biologic role of p63 in oral tumorigenesis and its possible role as prognostic marker in oral cancer. Ninety-four cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analyzed for p63 expression by immunohistochemistry. Normal oral mucosa showed a basal and parabasal expression of p63. Five (5.3%) cases of oral cancer showed less than 10% of positive tumor cells; in 33 (35.1%) cases the positive tumor cells comprised between 10% and less than 30%, in 36 (38.3%) cases the positive tumor cells comprised between 30% and less than 50%, and in 20 (21.3%) cases the positive tumor cells were more than 50%. There was also a statistically significant correlation between p63 expression and tumor differentiation: p63 expression was amplified in poorly differentiated tumors (P < .05). When analyzed for prognostic significance, patients with perineural infiltration had poorer survival rates than the group with no perineural infiltration (P < .05) and patients with increased p63 expression had poorer survival rates than the group with reduced p63 expression (P < .05). The statistical analysis showed no significant correlation between p63 expression, sex, age, tumor size, staging, recurrence, and metastasis. Cases with diffuse p63 expression were more aggressive and poorly differentiated and related to a poorer prognosis. These data suggest that p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.
Abstract: PURPOSE: Candida albicans is a component of the normal oral microflora, but local and systemic factors can transform this commensal C albicans to a pathogen. The most frequent cause of Candida opportunistic infections (candidiasis) is dentures, especially if poorly fitting or poorly cleaned. Management of oral candidiasis depends on an accurate diagnosis, identification and elimination of predisposing factors, and, often, use of antifungal agents. The aim of this study was to examine fingernail varnish, currently used for onychomycosis therapy, to reduce the fungal colonization in prosthetic biofilms. MATERIALS AND METHODS: A varnish containing 5% amorolfine was applied once or twice a week for 6 months in six patients affected by nystatin-resistant denture-related stomatitis. In all six patients, the prostheses had previously been removed at night, and daily antimycotic topical therapy with nystatin had failed to resolve the stomatitis; after 30 days, these patients all showed persistence of candidal stomatitis. RESULTS: After 1 month, five of the six patients were negative for Candida; this situation was unchanged in the following monthly controls. Only in the patient with suspected Sjögren syndrome was oral Candida found 15 days after the last varnish application. None of the patients had any complaints about the medication. CONCLUSION: This varnish containing 5% amorolfine, applied once or twice a week for 6 months, was able to suppress the nystatin-resistant denture-related stomatitis.
Abstract: WNT-1 has been demonstrated to play an important role in the carcinogenesis of some cancers, but its significance in oral squamous cell carcinoma (OSCC) has not yet been elucidated. We investigated the WNT-1 expression in OSCC, its role on the expression of beta-catenin and its relation to Ki-67 and tumor differentiation. Surgical specimens from 82 OSCC patients were examined for WNT-1, beta-catenin, E-cadherin, gamma-catenin and Ki-67 expression by immunohistochemical staining. The results were compared with the clinicopathological data and the relationships were correlated. WNT-1 expression was low in 39 cases, moderate in 5 cases, and high in 38 cases. WNT-1 showed a significant association with the expression of beta-catenin, E-cadherin, gamma-catenin and Ki-67. It was significantly correlated with tumor differentiation. The results of this study showed that WNT-1 expression is correlated with beta-catenin, Ki-67 and tumor differentiation, which suggested that WNT-1 might play an important role in the disturbed differentiation and uncontrolled proliferation during OSCC carcinogenesis.
Abstract: AIMS: To evaluate the occurrence of professional delay in the diagnosis, referral, and treatment of patients with burning mouth syndrome (BMS). METHODS: Fifty-nine patients (51 women and 8 men; average age, 60.5 years; age range, 32 to 88 years) diagnosed with BMS at our institution were retrospectively studied. Data were collected about the onset of oral symptoms, consultations with medical and dental practitioners, and misdiagnosis before definitive BMS diagnosis and treatment. RESULTS: The average delay from the onset of the symptoms to definitive diagnosis was 34 months (range, 1 to 348 months; median, 13 months). The average number of medical and dental practitioners consulted by each patient over this period and who initially misdiagnosed BMS was 3.1 (range, 0 to 12; median, 3). Candidiasis and aspecific stomatitis were the most frequent misinterpretations of the symptoms before appropriate referral. In about 30% of cases, no diagnosis of the oral symptoms was made or explanation given. CONCLUSION: Professional delay in diagnosing, referring, and appropriately. managing BMS patients occurred frequently in the group studied. No significant differences were found in the number of medical and dental practitioners who were consulted. Emphasis must therefore be placed upon educational efforts to improve health care providers' awareness of BMS. This should increase the rate of recognition and appropriate referral or treatment of patients with chronic orofacial pain due to BMS.
Abstract: BACKGROUND: Osteoblastoma is a benign bone tumor accounting for 1% of all bone tumors; it commonly involves the spine and the sacrum of young individuals, with less than 5% being localized to the posterior mandible. In view of its rarity in the maxilla and mandible, osteoblastoma is rarely diagnosed as such in the absence of interdisciplinary cooperation. METHODS: A retrospective study of four benign osteoblastomas was performed based on a review of the clinical, radiographic, and histopathologic features of all cases. RESULTS: The tumors involved the posterior mandible of young patients (age range, 10-21 years; two male and two female patients) and appeared as painful bone expansions. Radiologically, they were poorly defined, radiolucent/radiopaque lesions containing calcifications and not showing sclerotic borders or periosteal reactions. Histologically, they were composed of osteoid and woven bone surrounded by plump osteoblast-like cells with interposed fibroblasts, inflammatory cells, and red blood cells. All patients were disease free after prolonged follow-up. CONCLUSIONS: Osteoblastomas may be distinguished from other bone tumors, fibro-osseous lesions, and odontogenic neoplasms on the basis of integrated clinical, radiologic, and histologic features and usually manifest an indolent clinical course.
Abstract: OBJECTIVE: Malignant epithelial tumours arising in the jaws are very rare. Adenoid cystic carcinoma (ACC) represents approximately 7.5% of all carcinomas and only a few cases of intraosseous (central) ACC have been reported in the literature. MATERIALS: The salient clinico-pathological features of a case of ACC, bilaterally occurring in the mandible of a young caucasian woman who also had lung metastases are reported to appropriately characterize such unusual lesions and discriminate them from other tumours that more commonly affect the mandible. RESULTS: The patient presented with a painful swelling of the right retro-molar area and paraesthesia of the ipsilateral lower lip and radiological investigations disclosed bilateral radiolucent lesions of the mandible with unequivocal signs of malignancy but without intra-lesional calcifications or association with teeth roots or cystic component. Conventional histological examination disclosed typical ACC with solid and cribriform growth patterns and extensive infiltration of the adjacent tissues. CONCLUSIONS: The diagnosis of intraosseous malignant salivary gland type neoplasms is very difficult in view of their rarity and lack of specific signs and mainly achieved after histological examination and complete clinico-radiological work up. As surgical treatment of the patient was not indicated, due to extensive neoplastic disease, the patient is being controlled with multimodal treatment, including chemo- and radiotherapy and is alive with persistent disease 3 years after the original diagnosis.
Abstract: Squamous cell carcinoma is the most frequent malignant tumor of the oral cavity and often arises from premalignant lesions. Traditional methods used by the pathologist are subjective and lack the sensitivity to predict accurately which precancers may progress with time. Therefore, it is important to search for markers that may identify progression of premalignant lesions. Microarray technology can be use with this aim. Here, we define the genetic expression profile of lingual dysplasia (DS) progression. By using cDNA microarray containing 19.2K clones and a baseline of 11 normal tissues, we compared 5 mild and 4 severe DS. We identified 270 genes differentially expressed in normal tissue vs. mild DS (i.e. 161 up- and 109 down-regulated) and 181 genes differentially expressed in mild vs. severe DS (i.e. 63 up- and 118 down-regulated). The described genes cover a broad range of functional activities: (a) anti-oxidative, (b) DNA-repair, (c) inflammatory response, (d) cell-adhesion/mobility, (e) extracellular matrix depolymerization, and (f) cell-cycle regulation. The data reported better define DS progression and can help in classifying premalignant lesions.
Abstract: Mutations in the PTCH gene, the human homolog of the Drosophila patched gene, have been found to lead to the autosomal dominant disorder termed Nevoid Basal Cell Carcinoma Syndrome (NBCCS, also called Gorlin Syndrome). Patients display an array of developmental anomalies and are prone to develop a variety of tumors, with multiple Basal Cell Carcinomas occurring frequently. We provide here the results of molecular testing of a set of Italian Nevoid Basal Cell Carcinoma Syndrome patients. Twelve familial patients belonging to 7 kindreds and 5 unaffected family members, 6 non-familial patients and an additional set of 7 patients with multiple Basal Cell Carcinoma but no other criteria for the disease were examined for mutations in the PTCH gene. All of the Nevoid Basal Cell Carcinoma Syndrome patients were found to carry variants of the PTCH gene. We detected nine novel mutations (1 of which occurring twice): 1 missense mutation (c.1436T>G [p.L479R]), 1 nonsense mutation (c.1138G>T [p.E380X]), 6 frameshift mutations (c.323_324ins2, c.2011_2012dup, c.2535_2536dup, c.2577_2583del, c.3000_3005del, c.3050_3051del), 1 novel splicing variant (c.6552A>T) and 3 mutations that have been previously reported (c.3168+5G>A, c.1526G>T [p.G509V], and c.3499G>A [p.G1167R]). None of the patients with multiple Basal Cell Carcinoma but no other criteria for the syndrome, carried germline coding region mutations.
Abstract: Sjögren's syndrome (SS) is a systemic autoimmune exocrinopathy that affects mainly the salivary and lacrimal glands, leading to progressive reduction in saliva and tear flow. Although the underlying immuno-mediated glandular destruction is thought to develop slowly over several years, a long delay from the start of the symptoms to final diagnosis has been frequently reported. A limited knowledge concerning SS natural history is among the major causes of the actual diagnostic delay. Although very few studies have been focused on the analysis of SS early clinical onset, a series of oral features preceding xerostomia/hyposalivation development in patients eventually diagnosed as having SS have been reported. Sialochemistry alterations, salivary gland swelling, early dental loss and sialorrhea have been observed before the onset of typical signs and symptoms (namely xerostomia and/or hyposalivation), which usually lead to SS clinical presentation and diagnosis. Here we suggest, after evaluating available data, that the traditional 'untouchable' association between SS and xerostomia/hyposalivation might probably be reconsidered, and that astute clinicians should not underestimate the possible presence or development of SS in patients without xerostomia/hyposalivation and presenting these atypical early oral features.
Abstract: We have earlier reported that the inhibition of apoptosis in head and neck squamous cell carcinomas (HNSCC) is because of upregulated expression of Bcl-2, Bcl-X(L) and Survivin. Hence, we addressed the question whether antisense approach towards these inhibitors of apoptosis could restore the apoptosis in HNSCC. Further, we wanted to see whether chemotherapeutic efficacy of Cisplatin and Etoposide could be enhanced by using these drugs in combination with antisense oligonucleotides in human laryngeal carcinoma HeP2 and tongue carcinoma Cal27 cells. The effect of these antisense oligonucleotides was examined on the mRNA expression by RT-PCR and on protein expression by Western blotting. Apoptosis was measured by flowcytometry, TUNEL assay and caspase-3 activity assay. Treatment of HeP2 and Cal27 cells with 400 nM antisense oligonucleotides against Bcl-2, Bcl-X(L) and Survivin for 48 hrs decreased their expression both at the mRNA as well as at the protein level, resulting in the induction of apoptosis. Treatment of HeP2 and Cal27 cells with these antisense oligonucleotides augmented Cisplatin and Etoposide induced apoptosis. Our findings emphasize the importance of Bcl-2, Bcl-X(L) and Survivin as survival factors in HNSCC cells. Antisense treatment against these survival factors in combination with lower doses of chemotherapy offers potential as a less toxic chemoadjuvant therapy.
Abstract: Bipolar disorder (BD) is a psychiatric disease characterized by recurrent and alternated episodes of depression and mania. For the treatment of BD, anticonvulsants drugs as lithium, carbamazepine and oxcarbazepine can be used. These drugs can be associated with potential adverse effects: weight gain, tremors, thyroid abnormalities, and cognitive, gastrointestinal, cardiac or dermatological problems. We describe a case of BD with oral lichenoid drug reaction probably because of the mood stabilizers.
Abstract: Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clincopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (P<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.
Abstract: Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered (p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects (p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV-negative than in HPV-positive OSCC [root mean-square error (RMSE) = 5.89 x 10(-6), % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV-positive cases (OR = 0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV-negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers.
Abstract: One case of aspergillosis and mucormycosis occurring in a patient with stage-IV Castleman disease was investigated. The patient, who had undergone polychemotherapy and was in otherwise good general condition, without lymphadenopathies or imbalance of the immune system, presented with a palatal ulceration that progressively involved the palatal mucosa and bone, the paranasal sinuses and the orbit. Repeated cultural examinations were always negative. He had undergone multiple cytological smears of the inflammatory infiltration and biopsies of both the oral and nasal mucosa, which resulted in extensive necrotic debris and suppurative inflammation, and, on the very last biopsy, fungal hyphae, spores and conidia were also detected. These were large, branching, mostly non-septate hyphae, associated with conidiophores and conidia, the latter appearing dark brown to black in the histological preparations. Following the diagnosis of combined mucormycosis and aspergillosis, the patient underwent prolonged topic and systemic antibiotic treatment that resulted curative. Mucormycosis usually is a fatal complication of head and neck or systemic disorders, leading to severe immune suppression. Nevertheless, early diagnosis may be achieved using a combination of special stains and may lead to effective antibiotic treatment and cure of the patient, even if associated with other opportunistic infections, such as aspergillosis.
Abstract: The oral mucous membrane has features similar to skin but also differs in several ways. This paper reviews the aspects of epithelial biology necessary for an understanding of the vesiculoerosive disorders.
Abstract: BACKGROUND: Recent data have shown a significant association between phosphorylated-Akt (p-Akt) and failure of local disease control by radiation therapy in head and neck squamous carcinoma (HNSCC), and also that Akt activation correlates with histologic progression of HNSCC from premalignant lesions to invasive cancer. This study evaluated the role of Akt in previously untreated preneoplastic lesions of oral cavity and invasive tongue carcinoma on patient outcome and cancer development. METHODS: PKB/Akt activation was assessed by immunohistochemistry using a phosphorylation state-specific antibody (Ser 473) in tongue cancer and preneoplastic specimens of oral cavity. RESULTS: The expression of p-Akt was detected in 24 (46%) of the 52 available tongue cancer cases and in 10 (45%) of the 22 available preneoplastic lesions. In tongue cancer, with a median follow-up of 7.3 years, p-Akt was highly expressed in the cases that relapsed (15 of 17, 88%) or died of cancer (10 of 12, 83%). Disease-free survival was significantly shorter in cases with Akt expression (log rank test, P < 0.0001) independently of the stage and nodal status. CONCLUSIONS: Expression of p-Akt correlated with worse outcome in patients with tongue cancer. This finding highlights the potential role of Akt as a prognostic marker and as a potential target for molecular therapeutics.
Abstract: A series of 66 cases of oral squamous cell carcinoma (OSCC) was retrospectively analyzed by immunohisto-chemistry for bcl-2 expression to verify its predictive value for clinical outcome in patients with OSCC. After grouping for bcl-2 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. Univariate and multivariate (Cox regression) analyses were performed. Thirty-six OSCC (54.5%) showed expression for bcl-2, whereas 30 (44.5%) were negative. No statistical association was found between bcl-2 expression and any variables considered at baseline. Overall disease-specific survival rate at 72 months was 51%, independently from the extent of the tumor. In terms of prognostic significance, the bcl-2-positive group showed more than 60% survival at 72 months whereas the bcl-2-negative group showed none. An independent association of bcl-2 expression was found with an improved overall survival rate (p = 0.048), although grading and staging were established to be the best baseline markers of prognosis. On the basis of these results, it is possible to suggest bcl-2 as an early marker of prognosis: lack of bcl-2 expression could constitute a hallmark of aggressive biological behavior in OSCC.
Abstract: The gastroesophageal reflux (passage of gastric contents into the oesophagus and the mouth) is the main sign/symptom of a very frequent gastroesophageal reflux disease. Thus, acid regurgitation originates from stomach and it is responsible of the onset of typical symptoms and mucosal injury. Also in oral cavity the noxious acid agent is able to injury oral cavity (soft and hard tissues). These effects are described from international literature, even if a greater interest has shown to date only for hard tissue injury.
Abstract: A series of 78 cases of oral squamous cell carcinoma was analysed by immunohistochemistry for expression of survivin, a recent apoptosis inhibitor. All cases were positive for survivin expression and were divided into two groups using a system of scores. Disease-specific survival curves were calculated according to Kaplan-Meier algorithm, and log rank test was used to compare survival curves. Then, Cox regression analysis was applied to determine the single contribution of covariates on survival rate. So, Cox analysis allowed us to detect the variables most associated to survival. Among the studied variables, such as grade of differentiation, tumor size, stage, recurrence of disease, lymph node presence, only stage and recurrence of disease were predictors of outcome; however, when we analyzed the survival without considering recurrence (that was the stronger predictor of death), a stepwise Cox analysis showed that Survivin, stage and grade of differentiation are significantly associated to survival, with a higher value for Survivin. These data suggest that survivin expression may identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype and, therefore, could influence the decision for the therapy at the time of diagnosis.
Abstract: The molecular mechanisms involved in the development of oral squamous cell carcinomas (OSCC) are not yet well understood. Evidence of recent studies suggests that aberrant beta-catenin signalling may participate in the neoplastic transformation and that it is implicated in the development of several tumours. Beta-catenin is a component of the catenin family and plays a crucial role in cadherin mediated cell adhesion. However, it has recently been shown that beta-catenin is also involved in other functions such as intracellular signalling and the regulation of gene transcription. The aim of this study is to evaluate the presence of mutation in exon 3 of the beta-catenin gene in 20 OSCC cell lines. DNA was extracted using Qiagen Qiamp DNA minikit and a region encompassing the exon 3 of beta-catenin gene was amplified using a single PCR assay. The PCR products were analysed by SSCP and direct sequencing to detect any mutation of the gene. Most of the cell lines examined showed, by immunofluorescence, a beta-catenin delocalization. SSCP and sequence analysis of the PCR products did not show any mutation of the beta-catenin gene in any of the cell lines. In conclusion, although aberrant expressions or abnormal localization of beta-catenin have been detected in several OSCC cells, it appears that this finding has no relationship with beta-catenin gene mutations.
Abstract: Tranbsuccal drug administration is an attractive method, as it has several advantages especially with respect to peroral delivery. Here we report: i) the aptitude of carbamazepine (CBZ) to penetrate porcine buccal mucosa and reconstituted human oral (RHO) epithelium; ii) three different tablet formulations for transbuccal administration; iii) the drug release rate from tablets. CBZ permeation through the buccal mucosa was investigated by using two different bi-compartmental open models: Franz cells for porcine buccal mucosa and Transwell diffusion cells system for RHO epithelium. Results, expressed as drug flux (Js) and permeability coefficients (Kp), indicated that CBZ well penetrates the membrane and arrives in the acceptor phase. Js and Kp resulted 7x10(-2) mg/cm2h and 0.23 cm/h for in vitro experiments and 1.81 x 10(-2) mg/cm2h and 4.57 x 10(-2) cm/h for ex vivo experiments. The flux is extensively affected by the membrane thickness. The CBZ release from three different formulations of tablets, prepared with loaded microspheres, loaded matrices, and conventional compressed physical mixture of components was studied. Using the new formulated "non-conventional" tablets prolonged drug release was obtained. Loaded matrix tablets discharged CBZ faster than microsphere tablets (17% and 12% in about 2.5 h respectively). Results indicate the possibility of administering CBZ on buccal mucosa.
Abstract: Scientific interest in saliva as a diagnostic matrix has greatly increased over the last decade. The Triage screening test (Biosite Diagnostics), a rapid immunological test used to detect recreational drugs in the urine, was used to compare two biological matrixes: a non-conventional one, saliva, and a traditional one, urine. Twenty-one drug abusers collected one urine and one saliva specimen, both of which were tested with the Triage kit. Data were validated by gas-chromatography-mass-spectrometry (GC-MS). Results were positive for methadone in 9 saliva and 14 urine specimens, for opiates in 2 and 10, respectively, and for barbiturates in 2 specimens. Saliva specimens were negative for cannabis, THC, benzodiazepines and tricyclic antidepressants, although the GC-MS analysis revealed low concentrations of these drugs in the saliva. The study demonstrates the possibility of using saliva as a diagnostic matrix to test for drug-taking; however, the Triage kit must be improved before being used with saliva.
Abstract: BACKGROUND: The aim of the present study was to evaluate microvessel density (MVD) in the cellular layers of ovarian endometriomata, with particular interest in the relationship with VEGF and survivin expressions by endothelial cells and with the diameter of the cysts. MATERIALS AND METHODS: MVD and VEGF and survivin endothelial cell expressions were evaluated in 26 ovarian endometriotic cysts and correlated with the cyst diameter. RESULTS: The mean MVD was higher in the inner specialized stroma of ectopic endometrium than in the outer fibrous capsule, but only in the fibrous capsule was MVD correlated with endothelial cell VEGF and survivin expressions as well as with the cyst diameter. CONCLUSION: The diameter of ovarian endometriotic cysts seems to be related to the angiogenic process involving the outer fibrous capsule, and not the inner specialized stroma of ectopic endometrium, since only in the capsule are vessels stimulated to proliferate by VEGF and protected from apoptosis by survivin, and their density is correlated to cyst diameter.
Abstract: BACKGROUND: P-cadherin (P-cad) is a transmembrane molecule involved in the cell-cell adhesion and similar to E-cadherin (E-cad), but less investigated in oncology, especially in in vivo studies. Aims of the present study were to assess the prevalence of P-cad expression in oral squamous cell carcinoma (OSCC) and to verify whether P-cad can be considered a marker of prognosis in patients with OSCC. METHODS: In a retrospective study, a cohort of 67 OSCC patients was investigated for P-cad expression and its cellular localization by immunohistochemistry; some respective healthy margins of resection were similarly investigated as standard controls. After grouping for P-cad expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, Staging, and overall survival rate. Univariate and multivariate analyses were performed. RESULTS: 37 cases (55.2%) of OSCC showed membranous/cytoplasmic positivity for P-cad, whereas 30 (44.8 %) were negative. Although with some differences in membranous vs cytoplasmic localization of P-cad in OSCC with different G, no statistical association was found between P-cad expression and any variables considered at baseline. In terms of prognostic significance, P-cad non expression was found to have an independent association with poorer overall survival rate than P-cad expressing group (P = 0.056); moreover, among P-cad +ve patients the best prognosis was for those OSCC with membranous (P < 0.0001) than those with cytoplasmic P-cad expression. CONCLUSION: On the basis of these results, it is possible to suggest P-cad as an early marker of poor prognosis. The abnormal or lack of P-cad expression could constitute an hallmark of aggressive biological behavior in OSCC.
Abstract: Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR < 0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR < 0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying pre-malignant lesions and tongue SCCs.
Abstract: A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. In RCs p63 positivity was not only in basal and parabasal layers but also in the intermediate layer and about 1/3 of cases displayed a percentage of stained cells comprised between 0 and <5%, and about 2/3 between >5% and <50%. In FCs positivity was confined to basal and parabasal layers of the epithelium and in the majority of FCs the stained cells were comprised between 0 and <5%. OKCs displayed the most intense and diffuse p63 labeling. In conclusion, these data suggest that p63 expression may be useful to identify cysts type with more aggressive and invasive phenotype supporting the hypothesis of a suprabasal proliferative compartment in OKCs.
Abstract: Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It is now quite evident that a number of sub-epithelial vesiculobullous disorders may produce similar clinical pictures, and also that a range of variants of MMP exist, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated sub-epithelial blistering diseases (IMSEBD) has therefore been used. Immunological differences may account for the significant differences in their clinical presentation and responses to therapy, but unfortunately data on this are few. The diagnosis and management of IMSEBD on clinical grounds alone is impossible and a full history, general, and oral examination, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. No single treatment regimen reliably controls all these disorders, and it is not known if the specific subsets of MMP will respond to different drugs. Currently, apart from improving oral hygiene, immunomodulatory-especially immunosuppressive-therapy is typically used to control oral lesions. The present paper reviews pemphigoid, describing the present understanding of this fascinating clinical phenotype, summarising the increasing number of subsets with sometimes-different natural histories and immunological features, and outlining current clinical practice.
Abstract: The family of the poly(adenosine diphosphate-ribose) polymerase (PARP) proteins is directly involved in genomic stability, DNA repair, and apoptosis by DNA damage. In this study, we evaluated the role of PARP-1 in melanoma and its prognostic importance. We studied by immunohistochemistry and Western blot analysis PARP-1 expression in a selected series of 80 primary melanoma of the head and neck region. The results were correlated with tumor thickness and patient's outcome. A follow-up of at least 3 years was available. Fifteen cases of benign melanocytic nevi were used as controls. Normal melanocytes showed only scattered, focal nuclear positivity and were considered as negative for PARP-1 expression by immunohistochemistry (score, 0). Thirty cases of melanoma (37.5%) showed nuclear expression of PARP-1 in both radial and vertical growth phases. Western blot analysis showed the presence of a high signal for full-length PARP-1 only in the cases with high immunohistochemical (nuclear) expression of protein (score, ++/+++) in both radial and vertical growth phase. A significant correlation was present between PARP-1 expression in vertical growth phase and the thickness of tumor lesion (P = .014); all but one tumor measuring less than 0.75 mm showed no or low PARP-1 expression. No correlation was found between PARP-1 expression in radial growth phase and tumor thickness (P = .38, data not shown). These data suggest that PARP-1 overexpression is a potential novel molecular marker of aggressive cutaneous malignant melanoma and a direct correlation between PARP-1-mediated inhibition of the apoptosis and biologic behavior of cutaneous malignant melanoma.
Abstract: The aim of this clinical report is to describe the management of a young patient, affected by ectodermal dysplasia, during a nine-year period. Dental treatment can vary depending on the severity of the disease (tooth size, morphology, and amount of available alveolar bone). New technologies, such as adhesive dentistry, and new materials, such as composite resin, represent current options in the management of the dental rehabilitation of patients affected by ectodermal dysplasia. Removable partial dentures were used to replace congenitally missing teeth, and composite resin materials were used to restore conical-shaped maxillary teeth to achieve a favorable esthetic result. This option minimized the sacrifice of healthy dental tissue. Prosthodontic and restorative treatment was provided for the psychological and social comfort of the young patient.
Abstract: To evaluate in oral leukoplakia the relationship between HPV infection and markers of apoptosis (bcl-2, survivin) and proliferation (PCNA), also conditionally to age, gender, smoking and drinking habits of patients, by means of Fuzzy neural networks (FNN) system 21 cases of oral leukopakia, clinically and histologically diagnosed, were examined for HPV DNA presence, bcl-2, survivin and PCNA expression. HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR: MY09-MY11/GP5-GP6), and the HPV genotype determined by direct DNA sequencing. All markers were investigated by means of standardised immunohistochemistry procedure. Data were analysed by chi-square test, crude OR and the 95% CI; in blindness, FNN was applied. HPV DNA was found in 8/21 OL (38.1%); survivin, PCNA, and tobacco smoking were associated in univariate analysis (p = 0.04) with HPV DNA status. HPV-18 was the most frequently detected genotype (6/8), followed by HPV-16 (2/8). FNN revealed that survivin and PCNA, both being expressed in all of OL HPV+ve, were associated with HPV infection. In conclusion, the FNN allowed to hypothesise a model of specific variables associated to HPV infection in OL. The relevance of survivin and PCNA suggest that they may be involved in HPV-mediated deregulation of epithelial maturation and, conversely, that HPV may have a role in the expression level of these two markers. FNN system seems to be an effective tool in the analysis of correlates of OL and HPV infection.
Abstract: In recent years an association between oral lichen planus (OLP) and HCV infection has been reported, but the frequency of this association seems to differ in the various geographic areas. It is clear, instead, that some abnormalities occur in the immune-regulation mechanisms of patients with OLP and it is thought to be due to the chronic antigenic stimulus of HCV that causes functional disorders of the immune system in infected patients. Possible immunologic difference between 17 patients with OLP and HCV+ and 17 patients with OLP and HCV- were investigated using standard immunofluorescence and flow cytometry techniques. The distribution of T and B cells was normal in all patients examined, while NK CD56+ cells were increased, above all in HCV- patients. About 65% of T CD4+ lymphocytes coexpressed the CD45RO isoform (p=0.002), while approximately 32% expressed CD45RA, without significant differences in comparison to HCV+ subjects (p>0.05). Moreover, almost all the CD4+CD45RO+ subpopulation coexpressed CD29 in all patients examined. No significant differences between the two groups of patients were detected as to the increase of cytotoxic T CD8+CD57+ lymphocytes. The B cells CD19+CD5+ responsible for the production of "natural" antibodies were detectable in both the examined groups, even if not in all HCV+ subjects (30% +/- 10.1 in HCV- and 27% +/- 19.4 in HCV+ patients; p=0.47). These findings suggest the existence of differences in lymphocyte subpopulations between OLP-HCV+ subjects and OLP-HCV- patients.
Abstract: BACKGROUND: As for rhabdomyosarcoma (RMS) of other anatomic regions, the evaluation of traditional clinicopathological parameters does not allow the unequivocal outcome prediction of the single cases of orbital RMS. We investigated the role of DNA ploidy and immunohistochemical expression of p53, bcl-2, MDR-1 and Ki67 (MIB1) in the prognostic evaluation of orbital rhabdomyosarcomas. MATERIALS AND METHODS: The study population consisted of 11 selected cases. Serial sections of each tumor, stained with Feulgen's technique, were analyzed for the DNA content, using the QUANTIMET 500c Leica analyzer, QWINVO200A software. The results were compared with the immunohistochemical expression of p53 (wild plus mutated, W&M and mutated), bcl2, MDR-1 and Ki67 (MIB1), and with follow-up data. RESULTS: The statistical analysis of results showed that the cases of tetraploid and/or multiploid RMS, overexpressing p53 (W&M and mutated) and MDR-1, were characterized by an overall worse prognosis. On the contrary, the tumors with a favourable clinical course showed hyperexpression of MIB1 and absence of mutated p53 expression. Significantly higher MIB1 expression was found in the relapse-free group of tumors, with respect to the RMS with relapse (both in primary tumors and relative relapses, p<0.05). This finding could justify the higher sensibility to pharmacological therapy of RMS of the first group. The group of RMS with a worse prognosis (primary tumors and relapses) showed instead p53 overexpression (W&M and mutated), MDR-1 expression and multiploidy, with high 5cEE values and tetraploid peaks. No significant difference was found concerning the expression of bcl-2 among the two groups of RMS (p>0.05). CONCLUSION: The evaluation of DNA ploidy, p53, MIB1 and MDR-1 expression could be used for subtyping of orbital RMS into two prognostically different subcategories, respectively RMS responder to the therapy, with favourable clinical outcome, and RMS with a worse prognosis, requiring more aggressive therapeutic protocols.
Abstract: OBJECTIVE: Bilateral and multiple lymphoepithelial cysts (LECs) of major salivary glands, in particular of parotid glands, are quite rare and have been reported in human immunodeficiency virus (HIV) infected patients with an incidence of about 3-6%. These lesions represent an early manifestation of HIV infection and are rarely found in patients with advanced acquired immunodeficiency syndrome. MATERIALS: Two cases of parotid LECs, the first occurring in a middle-age white woman and the second in a young white boy, both in advanced phases of HIV infection, are reported. RESULTS: Clinical, cytological, histological and immunohistochemical (cytokeratin AE1/AE3, CD20, CD45RA, CD8, kappa and lambda immunoglobulin light chains, S-100, MLA and Ki67) features are described. CONCLUSIONS: Fine needle aspiration (FNA), a relatively non-traumatic procedure, could represent both a diagnostic and a therapeutic tool in parotid LECs. No surgical therapy is usually required for these lesions and aspiration of cystic fluid with FNA is quite resolutive, although evidence of further relapses does exist. Surgical excision may become necessary when pain, because of persistent and progressive swelling of the parotid gland, occurs.
Abstract: PURPOSE: Several recent medical reports have focused attention on the possible application of skeletal scintigraphy imaging in odontostomatology. The aim of the present report was to assess the influence of immediate prosthetic loading on peri-implant osteoblastic activity through bone scintigraphy. MATERIALS AND METHODS: Implants were placed in 2 healthy women. A nuclear medicine investigation with single-photon emission-computed tomography (SPECT) was performed for both patients at 30 and 90 days after implant placement. The study was completed with acquisitions of planar images of the skull in an anterior view and the use of regions of interest (ROIs) of the same size in the area corresponding to immediate loading and in the opposite hemimandible (at the control sites). Count density ratios (counts/pixel) obtained from each ROI were used for a quantitative/relative assessment. Tomographic images were evaluated with a qualitative method. The spatial resolution of the reconstructed tomograms and of the planar images was approximately 7 mm. RESULTS: Routine planar methodology provided a direct measure of cellular activity of the examined areas. The difference in count density ratio registered from the same ROI between the first and the second scintigraphy revealed the course of peri-implant osteoblastic activity, which was very high in the first month and then declined during subsequent months. DISCUSSION AND CONCLUSION: In spite of the small number of involved patients, the results obtained from this pilot study suggest that nuclear medicine may hold possible advantages in implant dentistry for those who seek to clarify the still unknown aspects of osteoblastic activity.
Abstract: The association of chronic inflammation with a variety of epithelial malignancies has been recognised for centuries. Well established examples include, among many others, oesophageal adenocarcinoma associated with chronic oesophagitis and bowel cancer associated with chronic inflammatory bowel diseases. By now no data, other than clinical observation, have been available in understanding the pathogenesis of these inflammation-related tumours. However, recent molecular studies on the relationship between solid malignancies and the surrounding stroma have given new insights. There is now enough evidence to accept that the chronic inflammatory process per se is able to provide a cytokine-based microenvironment which is able to influence cell survival, growth, proliferation, differentiation and movement, hence contributing to cancer initiation, progression, invasion and metastasis. Here it is discussed whether also oral lichen planus (OLP), being a chronic inflammatory autoimmune disease which has been clinically associated with development of oral squamous cell carcinoma, might be categorised among these disorders. With this aim, we critically reviewed and detailed the presence, in OLP subepithelial infiltrate, of inflammatory cells and cytokine networks that might act to promote squamous tumorigenesis.
Abstract: This report was performed to study the biological role of c-Met in oral tumorigenesis by analyzing its expression in relation to clinicopathological features. Seventy-three cases of oral squamous cell carcinoma and 10 of normal mucosa were analysed for c-Met expression by immunohistochemistry. Normal oral squamous epithelium showed absent or low membranous positivity in the intermediate (malpighian-spinous) layer. Fifty-seven cases (78%) of carcinoma showed immunopositivity, with a prevalently membranous positivity and scattered areas also showing a cytoplasmic localization. Sixteen cases of carcinoma (22%) showed no positivity for c-Met. Among positive tumours, well-differentiated areas showed low or absent cytoplasmic positivity, while low-differentiated areas showed both membranous and cytoplasmic positivity. There was no statistically significant correlation between c-Met expression and sex, recurrence, staging or grading. The frequency of lymph node metastases was higher in c-Met-positive tumours (17/57, 29%) than in c-Met-negative ones (4/16, 25%). When analysed for prognostic significance, patients with negative/reduced c-Met expression had better survival rates than patients with high expression. The difference between survival rates was statistically significant (p<0.05). These data suggest that c-Met expression may be useful to identify cases of oral squamous cell carcinoma with a more aggressive and invasive phenotype.
Abstract: HSP27 belongs to the Heat shock protein (HSP) family, which plays essential functions in cells under physiological conditions and prevents stress-induced cellular damage. The aim of this study was to investigate the biological role of HSP27 in oral tumorigenesis. MATERIALS AND METHODS: Seventy-nine cases of oral squamous cell carcinoma and 10 cases of normal mucosa were analysed for HSP27 expression by immunohistochemistry. Moreover, the western blot analysis was performed on two cases of normal mucosa and five cases of OSCC. RESULTS: Normal oral mucosa showed a suprabasal expression of HSP27. Twenty-four cases of SCC (30.7%) showed a diffuse staining for HSP27, and 48 cases (60.3%) showed instead a decrease in staining, which was diffuse, homogeneous, or with alternation of positive and negative areas in a single tumor ("mosaic" pattern). Only 7 cases of OSCC (7.5%) were completely negative for HSP27. Frequency of lymph node metastases was higher in HSP27-negative tumours (3/7, 42.8%) than in HSP-reduced (16/48, 33.3%) or positive ones (5/26, 19.2%). Regard staging, stages I and II had a higher score than stages III and IV (stage I > stage II > stage III > stage IV). There was also a statistically significant correlation between HSP27 expression and grade: HSP27 expression was reduced in poorly differentiated tumours (P < 0.05). When analysed for prognostic significance, patients with negative/reduced HSP27 expression had poorer survival rates than the group with positive HSP27 expression (P < 0.05). The statistical analysis of these findings showed no significant correlation between HSP27 expression, sex, and tumour size. CONCLUSION: Cases with reduced expression were more aggressive and poorly differentiated. These data suggest that HSP27 expression may be useful in order to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers.
Abstract: Apoptosis must be considered a rescue mechanism that controls the integrity of the cell erasing aberrant clones and it is likely that failure of apoptosis constitutes a key factor responsible for tumour formation, progression and resistance to drugs. Several genes (e.g. survivin, bcl-2 family, p53) are involved in these pathways. Much work still needs to be done to identify the molecular pathway of apoptosis resistance but restoration of the apoptotic response represents a crucial new therapeutic target for cancer treatment.
Abstract: Hydroxyurea (HU) is commonly used for the treatment of chronic myelogenous leukaemia, polycythemia vera and essential thrombocythaemia. Patients receiving HU present a number of side-effects including skin/mucosa changes and tumours. Mucocutaneous abnormalities include xerosis, ichthyosiform lesions, dark brown pigmentation of skin folds and nails, malleolar ulcers, oral mucositis and oral ulcers. Cutaneous squamous/basal cell carcinomas have also often been reported following long-term administration of HU. HU-induced carcinogenesis is due to both the mutagenic potential of this agent and to an impairment of DNA repair mechanisms after damage by external factors such as ultraviolet radiation. Oral cancer following long-term treatment with HU has been reported only once, in a patient with concomitant multiple skin tumours. We present the unique case of a patient with polycythemia vera who developed oral cancer after 15 years of HU therapy.
Abstract: Liposarcoma, first described by Virchow in 1857, is the second most frequent sarcoma of soft tissues, although it is rare both in the head and neck and the oral cavity. Intra-orally, liposarcoma has been reported in the jawbones (particularly the maxilla) and the soft tissues -- mainly the cheek and floor of mouth, but it is rare in the tongue. A case of well-differentiated, superficial liposarcoma circumscriptum of the tongue is reported. The authors underline the difficulties in the clinical and histopathological diagnosis, as this tumour may be confused with lipoma. In view of the indolent behaviour of this tumour type, local recurrence or metastasis rarely occur; consequently, conservative surgical therapy is advised without adjuvant chemo-radio therapy.
Abstract: 27 kDa Heat shock protein (Hsp27), which is also identified as p29 estrogen-receptor associated protein, plays a crucial role in specific growth stages. It also seems to be involved in the balance between differentiation and apoptosis. To determine whether Hsp27 is involved during craniofacial development and odontogenesis, its expression was studied through immunohistochemistry of developing jaw bone as well as the odontogenesis of heads from human fetuses. Formalin-fixed paraffin-embedded specimens of 7 human fetuses (3 female, 4 male), obtained from miscarriages occurring between the 9th and 16th weeks of pregnancy, were examined by using a monoclonal antibody against Hsp27. Staining intensity (weak, +; moderate, ++; strong, +++) was evaluated semiquantitatively. The sample slice was cut through a coronal plane, which included eyes, nasal cavities, tongue, and primitive dental lamina with tooth germs. A transient and spatially restricted expression of Hsp27 in developing human jaw bones and teeth was observed. Osteoblasts around the uncalcified bone matrix showed Hsp27 immunoreaction products (+++), whereas osteocytes were not immunolabeled. In mandibular condyle, immunolabeling was restricted to hypertrophic chondrocytes (++). In developing tooth germs, Hsp27 immunostaining was detected throughout the bud (+++). At the early cap stage, a strong immunolabeling for Hsp27 was seen in the dental lamina (+++), and a moderate staining was seen in the outer dental epithelium (++). At the late cap stage, Hsp27 expression was detected in the outer dental epithelium (++) as well as in the cells of the future stellate reticulum (++). The spatiotemporal-restricted expression of Hsp27 in craniofacial bones during development suggests that this protein could be involved in the balance between differentiation and apoptosis, by modulating the viability of osteoblasts and chondrocytes. The specific regional and temporal expression patterns of Hsp27 during tooth development sustains that this small Hsp might be related to the morphogenesis and cytodifferentiation processes of tooth germs.
Abstract: HPV has been thought to be involved in the development of several oral diseases, such as premalignant mucosal lesions and oral carcinoma. Survivin is a recently characterized IAP protein, which is abundantly expressed in most solid and haematological malignancies, but undetectable in normal adult tissues. Aim of this study was to investigate survivin expression and HPV presence in oral premalignant lesions and oral carcinoma. 47 samples of oral tissue including 11 squamous cell carcinomas (OSCC), 16 oral leukoplakias (OL) and 20 normal oral mucosa specimens, after investigation of HPV presence by nested PCR (consensus MY/GP primers) and viral genotype identification by direct sequencing were investigated by immunohistochemistry to detect survivin expression. Survivin expression was evident in 4/7 (57.1%) HPV+ and 4/4 (100%) HPV- OSCC, 6/7 (85.7%) HPV+ and 5/9 (55.5%) HPV- OL and in 0/20 (0%) control samples. Data showed high levels of survivin expression in HPV-positive SCCs, even if mean values were lower than HPV-negative ones, which in particular showed survivin expression in 100% of cases. Conversely, survivin expression was greater in HPV+ precancerous lesions than in HPV- ones. Our findings suggest that survivin may be involved in HPV- mediated deregulation during maturation of squamous epithelium through modulation of the apoptotic processes and, conversely, HPV may have a direct or indirect effect on the regulation of the survivin expression level. In particular, the results of this study suggest distinguishing between cancerous and precancerous oral lesions with respect to survivin expression when HPV infection is present. The most unfavourable behaviour is likely to be for the HPV- OSCC.
Abstract: The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disease characterized by numerous basal cell carcinomas, odontogenic keratocysts of the jaws, palmar and plantal pits, skeletal abnormalities, and calcification of the falx cerebri. The gene responsible for this syndrome is the PTCH tumor suppressor gene encoding for the sonic hedgehog receptor. In this paper, we report thirteen novel mutations identified in the first screening of NBCCS patients in Italy. Except for p.T230P and p.F505_L506delinsLR, all the other mutations are predicted to determine a premature truncation of the protein.
Abstract: Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinoma (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed ones. From this study as well as from other works, it appears that indeed COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.
Abstract: Granular cell tumor (GCT), or granular cell myoblastoma, is a relatively uncommon lesion of the soft tissues. It can occur in any organ, and the tongue is more often affected. GCT has unknown etiology, uncertain histogenesis, and a not always benign nature. Benign myoblastomas are the great majority, but rare malignant lesions have been reported. To have more information regarding the genetic events involved in GCT, the authors decided to perform an expression profile. A sample was derived from a surgically resected GCT of the tongue. RNA extracted from normal tongue (mucosa plus muscle) was used as control. By using DNA microarrays containing 19,200 genes, the authors identified several genes for which expression was significantly up- or down-regulated. The differentially expressed genes cover a broad range of functional activities: (1) signal transduction, (2) cell cycle regulation, and (3) cytoskeleton organization. It was also possible to detect some genes whose function is unknown. The data reported are, to the authors' knowledge, the first genetic portrait of GCT. Mutations in some of the described genes are related to neural alterations and mental diseases, and this fact supports the idea of a neural origin of myoblastoma. Several markers have been identified that will help in identifying the biological behavior (when malignant lesions will be described), as well as the gene whose products could be potentially disease-specific targets for therapy.
Abstract: The mechanisms employed by human papillomaviruses (HPVs) to control the replication of the viral genome and the expression of the viral genes are extremely complex and further complicated by the fact that the viral life cycle is intricately tied to the differentiation program of its host epithelial tissue. Indeed, HPV-induced immortalization of keratinocytes and disruption of the normal cytokeratin (CK) expression pattern progress pari passu during the stepwise process that preludes to squamous cell carcinoma. In our study, we have analyzed the interaction occurring between HPV type 16 E7 mRNA and the intermediate cytokeratin filaments 7 and 19 and report data in favor of a possible association between HPV16 E7 protein level and CK19.
Abstract: P-cadherin, a transmembrane molecule similar to E-cadherin involved in the cell-cell adhesion, and catenins form complexes between its cytoplasmic domain and the cytoskeleton. Five cell lines, 108 specimens of oral squamous cell carcinomas (OSCC), 9 metastasis and 10 of normal oral mucosa were examined to evaluate P-cadherin expression and cellular localization by immunohistochemistry and western-blotting. In normal oral mucosa there was a membranous expression only in basal and parabasal layers. 91 cases (84%) showed membranous/cytoplasmic positivity, whereas 17 cases (16%) were negative. In particular, while well-differentiated carcinomas showed P-cadherin upregulation, the protein was homogeneously hypo- or unexpressed in low-differentiated carcinomas. There was a statistically significant correlation between P-cadherin expression and tumour grading: G3 tumours had a lower score than G1-G2 tumours (P<0.05). When analysed for prognostic significance, patients with no P-cadherin expression (score 0) had poorer overall and diseases-free survival rates than the P-cadherin-expressing group (score 1) (P=0.0463 and P=0.0471, respectively). Western blotting analysis of cell lines and tissue samples confirmed immunohistochemical findings. When cell staining pattern of positive cases was examined, 52 cases showed a prevalent membranous pattern, while 39 had a prevalent cytoplasmic pattern. Cases with prevalent cytoplasmic staining showed high rates of lymph node metastases (P>0.05), and regional relapse (P <0.05) and poorer survival rates than the group with prevalent membranous expression (P<0.0001). An absent P-cadherin expression could constitute a hallmark of aggressive biological behaviour in oral squamous cell carcinoma.
Abstract: BACKGROUND: The recurrent chronic orofacial swelling caused by orofacial granulomatosis (OFG) can cause significant cosmetic and functional problems but can be prevented if the disease is diagnosed early and promptly treated. Although the enlargement of the lips is described to be the most common presenting complaint, the clinical onset of OFG may be characterized by minor associated mucosal and neurological manifestations, making early diagnosis very difficult or, sometimes, merely presumable. PATIENTS AND METHODS: We retrospectively analyzed the clinical manifestations of 19 patients with OFG, who were examined at our institution between 1998 and 2002, in order to determine their initial manifestations and presenting symptoms. RESULTS: A total of 10 patients showed classical recurrent enlargement of the lips (six lower; four upper) as presenting symptom. In the other nine patients, OFG onset was characterized by transient unilateral facial nerve palsy (two cases), intraoral manifestations (two cases), recurrent swelling of the periorbital area (two cases), of the chin (one case), of the zygomatic area (one case), and of the cheeks (one case). CONCLUSION: Our data underlined that OFG onset could be frequently characterized by widely variable, multiform, and temporary clinical findings. Involvement of atypical sites of the orofacial region and presence of single minor manifestations may occur as presenting symptoms, often preceding the development of traditional clinical findings.
Abstract: A high density of blood vessels is found in specimens of temporomandibular joint (TMJ) disc at any stage of internal derangement of the joint, but the factors responsible for angiogenesis in the disc have not been described. The purpose here was to investigate, in human TMJ discs, the expression of vascular endothelial growth factor (VEGF), a multifunctional cytokine that contributes to angiogenesis. Specimens, free of significant morphological alterations and with varying degrees of disc tissue degeneration/regeneration, were studied by immunohistochemistry for VEGF in order to correlate immunohistochemical with histopathological findings. In normal discs and discs with minor pathological changes, fibroblast-like cells, fibrochondrocytes and chondrocyte-like cells were either not or only weakly immunostained by VEGF antibody. In disc specimens from internal derangement of the TMJ with significant tissue degeneration/regeneration, VEGF was consistently expressed. In these specimens, immunoreaction products for VEGF were observed both in the disc and in the endothelial cells of newly formed vessels. This VEGF immunolocalization is consistent with the stimulation of angiogenesis and the morphogenesis and differentiation of chondrocytes. Therefore VEGF expression by disc chondrocyte-like cells might reflect the action of the cytokine as an inducer of angiogenesis and as an autocrine signal for cells of the chondrogenic lineage.
Abstract: Apoptosis is a genetically determined process playing an active role in tissue size regulation, morphogenesis and removing damaged cells that could be potentially dangerous for their host. Several agents involved in apoptosis regulation, such as the bcl-2 family components, act as oncogenes and are involved in oral carcinogenesis. Aim of this study is to explore bcl-2 immunoreactivity in oral cancers and to assess its potential clinico-pathological implications. Ninety oral squamous cell carcinoma and 10 normal mucosal formalin-fixed, paraffin-embedded samples were analysed for bcl-2 expression by immunohistochemistry. Normal oral mucosa showed a cytoplasmic pattern of bcl-2 immunoreactivity in the basal cell layers. Seventy-four cases of carcinoma (83%) showed no immunoreactivity, at variance with 16 cases (17%) manifesting consistent cytoplasmic positivity. Overall, the peripheral cells of differentiating epithelial tumour islands were intensely stained, with decreasing immunoreactivity toward the centre of the neoplastic nests. Fully keratinised tumour cells showed inconspicuous or absent bcl-2 immunoreactivity. No statistically significant correlations could be demonstrated between bcl-2 immunoreactivity and the sex of the patients, tumour size and with the occurrence of lymph node metastases. Though a direct correlation was found between bcl-2 immunoreactivity and increasing tumour stage, this did not reach statistical significance. Furthermore, G1 and G3 tumours displayed higher percentages of bcl-2-positive cells in comparison with G2 neoplasms and the different distribution of bcl-2 immunoreactivity in G2 and G3 was statistically significant (p<0.05). Finally, patients with absent or low (scores 0 and 1) bcl-2 immunoreactive tumours manifested poorer overall survival rates in comparison with patients with moderate or high (scores 2 and 3) bcl-2 immunoreactive tumours but the difference was not statistically significant. In normal oral mucosa bcl-2 protein is selectively present in the basal cell layers and possibly participates in the control of the terminal keratinocytes differentiation. The study of bcl-2 immunoreactivity possibly may be useful for better characterising and predicting the prognosis of oral SCC but cooperative studies are needed to assess its applications in the clinical practice.
Abstract: BACKGROUND: Extracardiac rhabdomyomas are rare benign tumors of the head and neck. They are frequently misdiagnosed and possibly overtreated when confused with other aggressive tumors. METHODS: This article reports on the clinicopathologic features of two such tumors affecting adult patients and initially seen as slowly-growing, indolent neoplasms. RESULTS: The tumors were of fibrous consistency, mobile, with well-demarcated borders and evident lines of cleavage. Both patients were treated by conservative surgery and remained disease-free after prolonged clinical observation. Histologically, both tumors were composed of large eosinophilic cells intermingled with polyhedral clear cells. Both cell types contained abundant glycogen accumulations. CONCLUSIONS: The differential diagnosis is with granular cell tumor and with sarcomas, the former being easily distinguishable morphologically, and the latter be seen with more rapid growth and adherence to the adjacent tissues. On the basis of the preceding features, rhabdomyomas can be suspected at a preoperative stage and adequately managed with enucleation or simple excision.
Abstract: PURPOSE: This study evaluated the effectiveness of a protocol using platelet-rich plasma (PRP) to prevent bleeding after dental extraction in patients treated with anticoagulant oral therapy. MATERIALS AND METHODS: Forty patients with mechanical heart-value replacement who were treated with anticoagulant oral therapy were selected for the study. Each patient was treated with PRP gel placed into residual alveolar bone after extraction without heparin administration after suspension of oral anticoagulant drugs (36 hours). RESULTS: Only 2 patients reported hemorrhagic complications (5%). Sixteen patients (40%) had mild bleeding that was easy to control with hemostatic topical agents; this mild bleeding terminated completely 1 to 3 days after the surgical procedures. The remaining 22 patients (55%) presented with adequate hemostasis. CONCLUSIONS: Oral surgery in heart surgical patients under oral anticoagulant therapy may be facilitated with PRP gel. Its use is an advanced and safe procedure. This biological and therapeutical improvement can simplify systemic management and help avoid hemorrhagic and/or thromboembolic complications.
Abstract: BACKGROUND: Uveal malignant melanoma (MM) is characterized by a marked variability in biological behavior and by an unpredictable clinical course. Therefore the search for reliable prognostic parameters is active. In this study we investigated the immunohistochemical expression of cyclin D1, a cell cycle regulatory molecule, to analyze the possible significance of the protein in the prognostic evaluation of these neoplasms. MATERIALS AND METHODS: Forty-five selected uveal MM were incubated with the anti-cyclin D-1 antibody; the findings were compared with the follow-up data, with the cell type and with the largest tumor dimension. RESULTS: The overexpression of cyclin D1 was found to be inversely related to disease-free interval (p < 0.001) and to the spindle A/B tumors with good prognosis (p = 0.05). On the other hand, a direct correlation was found with epithelioid/spindle B melanomas with poor clinical course (p = 0.05) and with sclera infiltration (p = 0.01). No statistically significant relation emerged between cyclin D1 expression and LTD. CONCLUSION: These data may suggest a possible role of the overexpression of cyclin D1 in the tumorigenesis of uveal MM and in the prognostic evaluation of these tumors, representing a useful tool to subclassify lesions with similar morphological features.
Abstract: Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.
Abstract: A series of 110 cases of oral squamous cell carcinoma (SCC) together with six lymph node and one distant metastatic lesions was analysed for expression of survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven cases, 100%) were positive for survivin expression, with weighted survivin scores ranging from 1 to 4. In contrast, normal oral epithelium did not express survivin. There was no significant correlation between survivin expression and age, sex, tumour size, the presence of lymph node and distant metastases. Survivin expression was increased in poorly differentiated tumours, even if differences were not statistically significant. In contrast, when analysed for prognostic significance, patients with low survivin expression had statistically significant better survival rates than the group with high survivin expression (P<0.05). These data suggest that survivin expression may identify cases of oral SCC with more aggressive and invasive phenotype.
Abstract: Squamous cell carcinoma (SSC) is the most frequent malignant tumor of the oral cavity. Aberration of programmed cell death is thought to participate in cancer. Using specific antibodies a study of the expression and subcellular distribution of Bcl-2, BAX, caspase-3 and cytochrome c in normal human keratinocytes and mouth carcinoma slowly (HN) and rapidly growing (KB) cells has been carried out. In carcinoma cells depressed expression of BAX, presence in the cytosol of procaspase-3 and absence in this fraction of cytochrome c have been found. PGE2 treatment prevented cell growth depression induced by pro-apoptotic serum starvation both in control and carcinoma cell cultures. It is also shown that PGE2 promoted both in keratinocytes and KB cells expression of Bcl-2, which was accompanied in the first case by increase in its mitochondrial level. These results indicate that in carcinoma cells there is an apparent down regulation of the apoptotic cascade as compared to normal keratinocytes. Thus the possibility that down regulation of apoptosis is associated with promotion of tumor development in the oral mucosa cells seems to be supported by these observations.
Abstract: BACKGROUND: Leiomyosarcoma is a relatively uncommon mesenchymal tumor that exhibits smooth-muscle differentiation. Only 3 to 10% of leiomyosarcomas arise in the head and neck, the nose and paranasal sinuses, skin and subcutaneous tissue and cervical esophagus being the most common localizations. Most leiomyosarcomas involving the oral tissues primarily affect the maxillary sinus, the maxillary or mandibular bone. A review of the English-language literature since 1908 revealed 30 reported cases of primary leiomyosarcoma of the oral mucosa and soft tissues. MATERIAL AND METHODS: We report on a case of gingival leiomyosarcoma, arising in a 31-year-old female and involving the upper alveolar mucosa. Following the diagnosis of malignant neoplasm on frozen sections and an en-block resection, the tumour was formalin-fixed and paraffin embedded for histological and immunohistochemical examination. RESULTS: Microscopically, the tumor was composed of interlacing fascicles of spindle-shaped cells with elongated, blunt-ended nuclei and eosinophilic cytoplasm, containing PAS-positive granules. Mitoses, both typical and atypical, and scattered necrotic foci were present. Consistent desmin, muscle specific and alpha-smooth muscle-specific, and vimentin immunoreactivity was demonstrated in the tumor cells. The patient is alive and free of disease at a 7-year follow-up. CONCLUSIONS: Intra-oral leiomyosarcomas are exceptionally rare. Accurate diagnosis and treatment is largely based on the careful search of clinical signs indicative of malignancy (e.g., neoplastic bone destruction, wide invasion of adjacent tissues) and intra-operative (frozen sections) examination of the lesion. Though the case reported herein showed an attenuated clinical behavior, prolonged follow-up is mandatory in view of possible tumor relapse.
Abstract: The aim of this study was to evaluate HSP27 expression in fetal, normal and inflamed oral mucosal epithelium and in oral premalignant epithelial lesions and in their ensuing invasive cancers. In developing human oral epithelia, immunoreactions for HSP27 were moderately observed in suprabasal keratinocytes of palate and tongue. Normal oral epithelium had an intense suprabasal positivity. In inflamed oral mucosa, HSP27 staining was stronger in basal and suprabasal keratinocytes than in normal epithelium. Most oral premalignant lesions showed no (5 cases, 29%) or low (8 cases, 46.4%) staining. In OSCC both low and high HSP27 levels of expression were observed. HSP27 immunolabelling was down-regulated in poorly differentiated areas and up-regulated in highly differentiated ones. These findings indicated that HSP27 expression seems to protect cells from apoptosis during inflammation, while the down-regulation in dysplasia could impair the protective mechanism against mutagenesis induced by environmental factors and thus enhancing the transformation of oral epithelial dysplasia into OSCCs.
Abstract: p120(cat) is a novel component of the catenin family, a cytoplasmic molecule closely associated with the cell-cell adhesion molecule E (epithelial)-cadherin, by forming complexes between the cytoplasmic domain of E-cadherin and the cytoskeleton. Recent studies suppose a role for this molecule in human cancers and to date none report its expression in oral squamous cell carcinomas (SCCs). The goal of this study was to evaluate the role of this protein in the oral carcinogenetic process. A linked streptavidin-biotin-alkaline phosphatase technique was used to examine the immunoreactivity and cellular localisation of p120(cat) in five oral epithelial cell lines (NCTC 2544, normal and immortalized keratinocytes; KB, a poorly differentiated SCC cell line; OSC 20, a well differentiated oral SCC cell line; CAL 33 and CAL 27, moderately differentiated oral SCC cell lines) and 10 normal oral epithelium biopsies. RESULTS: As already reported for E-cadherin, beta- and gamma-catenin, p120 expression showed a homogeneous membranous localization in normal oral specimens. The intensity of staining for p120 progressively increased from basal and parabasal layers toward the intermediate spinous layer. No staining for p120 was observed in the upper layer. NCTC showed a membranous positivity. OSC 20, CAL 33 and CAL 27 showed a membranous positivity, even if polarized to cell-cell adhesion sites, in 40-50% of cells. OSC 20, CAL 33 and CAL 27 cells showed also a cytoplasmic delocalization. All positive KB cells showed a prevalent cytoplasmic staining and 10% of these cells showed a nuclear delocalization. In cancer cells, p120 showed an inverse relationship with the degree of differentiation for a progressive displacement of the signal toward the cytoplasm or nucleus in dedifferentiated cells. In conclusions, this nuclear delocalization for p120 could suppose its potential involvement in signalling and cancer transformation.
Abstract: The authors reviewed the clinical records and the histopathological preparations of 78 cases of Warthin's tumours (WTs), treated at the Department of Dental Sciences, Centre for the Study of Oral Tumours, of the University of Bari. All the surgical specimens had been fixed in neutral buffered formalin, sampled according to the step-serial, whole-specimen sectioning technique, embedded in paraffin and stained with haematoxylin-eosin, periodic acid Schiff and Gomori's reticulin. The results showed that Warthin's tumours characteristically affect the parotid gland, and most frequently arise in adults (mean age=57 years) and in males (95%). Multiple tumours were detected in 16 cases (20.5%), and five of these were bilateral (6.5%). One of the multifocal tumours involved an intra-parotideal lymph node and the laryngeal piriform sinus. In addition, 13 cases (16.6%) were associated with other malignancies. These data indicate that multiple (synchronous or metachronous) WTs may occur more frequently than previously reported. The high rate of multiple WTs detected in the current study may result from extensive and accurate sampling of these neoplasms for histopathological evaluation. Consequently, complete preoperative work-up of patients harbouring parotideal tumours consistent with or suspicious for WT is necessary. The work-up should include CT scans and/or magnetic resonance imaging of both parotid glands, to exclude the occurrence of multiple tumours, which may be clinically undetectable. Also, fine needle aspiration biopsy may be an accurate tool for excluding malignant neoplasms and for better planning subsequent surgical procedures. These usually consist in (bilateral) superficial parotidectomy and should be followed by long term follow up of the patients, in view of possible metachronous WTs, even after prolonged time intervals.
Abstract: BACKGROUND: The WNT gene family is a group of developmental genes involved in cell growth regulation, differentiation and organogenesis in both vertebrates and invertebrates. These genes are also involved in oncogenesis: beta-catenin, a component of the WNT pathway, has been reported to be involved in the genesis of numerous human cancers. WNT-1 pathway signaling is mediated via interactions between beta-catenin, a multifunctional protein playing an important role in cell-to-cell adhesion and gene expression, and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and determines its accumulation in the cytoplasm and nucleus. MATERIALS AND METHODS: In order to evaluate the role of WNT-1 in the neoplastic progression of basal cell carcinoma (BCC), an immunohistochemical and confocal study of its expression and its correlation with beta-catenin distribution was performed in 46 selected cases of BCCs of the head and neck region. RESULTS: While normal skin showed a WNT-1-positive staining only of the cutaneous annexa and a few cells in the basal/parabasal layers, the areas of de-differentiated BCCs showed a high granular positive staining (50-80% of cells). On the other hand, normal skin was characterized by an intense membranous staining for beta-catenin, with a progressive displacement of the signal toward the periphery of the cells. In BCC the absence of membrane localization and cytosolic staining for beta-catenin were detected in de-differentiated cases. A significant correlation (by Pearson's analysis) between overexpression of WNT-1 and free pools of beta-catenins was observed in these tumors. CONCLUSION: According to these data, the potential role of the WNT-1 gene in BCC seems to correlate with its ability to induce elevated cytoplasmic beta-catenin levels, suggesting that the WNT-1 gene can activate an intracellular signaling pathway involved in the process of cell transformation.
Abstract: BACKGROUND: High-dose intravenous (i.v.) methylprednisolone has been used therapeutically in severe blistering diseases to avoid the complications and side-effects of long-term orally administered glucocorticoid therapy. The aim of the study is to evaluate the capacity of methylprednisolone i.v. 'pulse' therapy to induce remission in the treatment of severe oropharyngeal pemphigus. METHODS: Twelve patients, all of whom had oropharyngeal severe pemphigus, were included in the analysis. There were eight women and four men whose ages ranged from 22 to 78 years (mean age: 50.75 years) with a disease duration of 1-3 months(mean duration: 55 days). In order to obtain a rapid clinical remission of extensive mucosal lesions, we performed 'pulse' therapy with intravenous methylprednisolone (30 mg/kg body weight to a maximum of 1 g per dose on each of 3-5 consecutive days)evaluating the clinical response and the short-term side-effects. RESULTS: Our therapy was generally safe and well tolerated with a very low rate of side-effects. All patients responded to i.v. methyl-prednisolone with evidence of a decrease in signs and symptoms within l week of commencing treatment and in all cases remission was observed after the second or the third cycle of 'pulse'. The most common adverse events during treatment were flushing and hyperglycaemia; in a few cases we observed a metallic taste in the mouth, pruritus, headaches ranging from mild to moderate, palpitations, mood alterations, insomnia and fatigue. CONCLUSIONS: High-dose 'pulse' administration of glucocorticoids is a potentially effective therapy to be considered in the treatment of patients with severe oropharyngeal pemphigus. Similar patients treated with conventional oral administered doses of prednisone or deflazacort had protracted courses requiring months of glucocorticoid therapy with no long-term remissions. However, further well-designed, long-term comparative trials are required to confirm this.
Abstract: Oropharyngeal cancer is estimated to be the ninth most common cancer worldwide. Its prognosis is largely dependent upon tumour-stage at the time of diagnosis. Stage I and II oropharyngeal cancers are characterized by a 5-year survival rate ranging from 70% to 90%, and the management of these early carcinomas is usually of short duration, easy and very cost-effective. On the other hand, the diagnostic evaluation, treatment and management of complications and recurrences of advanced stage oral tumours (stage III and IV) are often very long, complex and costly. They also have very poor prognosis with survival figures dropping to about 20%. Nowadays, most oropharyngeal cancers are detected at a late stage with an overall 5-year survival rate of around 45-50%, and with a conspicuous increase in treatment costs and a worsening of prognosis. Even if formal and comprehensive cost-effectiveness and cost-benefit analyses are not currently available in the oropharyngeal cancer literature, it seems clear that, in the care of these patients, the enormous consumption of resources is not associated with acceptable outcomes. New initiatives should be evaluated, planned and developed for the care of patients with oral and pharyngeal cancer. These strategies should be directed at prevention and early diagnosis in order to increase patient survival and quality of life and decrease the consumption of health care resources.
Abstract: Despite the use of stent implantation along with percutaneous transluminal angioplasty, the rate of restenosis in high-risk patients is still high. Some studies have proven the ability of platelet glycoprotein IIb/IIIa receptor antagonists to reduce peri- and post-procedural thrombotic complications in endovascular procedures. We present the case of a 62-year-old female with in-stent restenosis who was successfully treated with femoral artery angioplasty with a stent-in-stent technique and tirofiban administration.
Abstract: BACKGROUND: Recent studies have reported nuclear delocalization of plakoglobin in acantholytic pemphigus vulgaris cells. The objective of this study was to evaluate the role of plakoglobin in the pathogenesis of acantholysis in pemphigus vulgaris (PV) and its relation with the urokinase-type plasminogen activator receptor (uPAR) expression. MATERIALS AND METHODS: Plakoglobin and uPAR expressions were evaluated by immunohistochemistry in 22 cases of PV at various stages of the disease, and as controls in 18 specimens of skin/oral mucosa from healthy patients. RESULTS: Healthy skin/normal oral mucosa showed strong plakoglobin expression in the basal and spinous layers with prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of the epithelium. In PV patients, a progressive displacement of the plakoglobin signal toward the nucleus was found in 18/22 of the cases. Healthy skin/normal oral mucosa showed low uPAR expression with prevalent cellular membrane distribution. In the PV patients, strong uPAR expression was present in the acantholytic cells in 16/22 of the cases. There was direct correlation (p < 0.05) between the uPAR expression and nuclear plakoglobin. CONCLUSIONS: The uPAR overexpression in acantholytic PV may be considered a direct consequence of plakoglobin abnormal distribution. Nuclear delocalization of plakoglobin, a direct consequence of plakoglobin-Dsg-3 dissociation induced by PV IgG, probably induces uPAR overexpression. This evidence suggests a central role for plakoglobin in PV pathogenesis because of its delocalization toward the nucleus, which is the probable cause of the uPAR gene expression.
Abstract: Angiosarcoma of the head and neck is a rare malignant tumour that most commonly involves the skin and subcutis, particularly of the scalp. It has been reported in intra-oral locations very rarely. This study reports on the clinico-pathological features of four such cases, in elderly patients and manifesting an aggressive course. All patients were admitted for rapidly enlarging masses involving the hard palate, alveolar crest and retromolar trigone and displaying bone destruction in three cases. Morphologically, three cases were composed by bundles of spindle cells admixed with variably sized abortive vascular channels which only showed slit-like spaces separating large clusters of epithelioid cells. In all instances, intra-cytoplasmic vacuoles containing intact or fragmented red blood cells were distinctly evident. All neoplasms showed consistent CD 31 immunoreactivity and variable degrees of CD 34 and Factor VIII related antigen positivity and were responsible for the death of the patients, for local progression or lung metastases, within 6 months from the original diagnosis. Due to their rarity, angiosarcomas with intra-oral presentation may be diagnosed with difficulty, especially on small incisional biopsies. and their differentiation from spindle cell carcinoma, malignant melanoma, anaplastic lymphoma, malignant myoepithelioma and other sarcomas that more commonly arise at this site should be based on accurate immunohistochemical characterisation.
Abstract: AIMS: At present oral lichen planus (OLP) is classified among precancerous conditions but very few data are available in literature regarding prognosis of OLP-related cancers. The aim of this paper is to evaluate clinical long-term behaviour of OLP-related oral squamous cell carcinomas (OSCCs). METHODS: Clinical history and data from follow-up regarding 21 patients undergoing malignant transformation of OLP have been critically revised. RESULTS: In a mean time of 2.6 years from diagnosis of OLP, patients developed OSCCs. Histopathologically, two carinomas showed a moderate degree of differentiation, while the others were well differentiated. Six (28.5%) were in situ OSCC, in eight (30%) was found a microinvasive pattern of infiltration, one was a stage II tumour and the remaining (6 cases) were stage I tumours. During follow up, four patients (19%) have developed another OSCC in a mean time of 11 months from the first occurrence. In two men (10% of cases), multiple OSCCs occurred and in five cases (24%) lymph nodal metastases were detected. CONCLUSIONS: Our study points out an alarming tendency in developing second primary metachronous tumours (33.3%) of the oral cavity and nodal metastases (23.8%), especially if we consider their early stages. Thus we always recommend a strict follow-up of OLP patients with clinical oral and neck examination every 2 months for 6-9 months since OSCC diagnosis is made and, after, three times a year.
Abstract: Deregulated expression of inhibitors of apoptosis (programmed cell death) may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to therapy. In this study, we investigated the potential expression and prognostic significance of the apoptosis inhibitor survivin in squamous cell carcinoma (SCC). A series of 135 cases of SCC including 46 oral SCC and 89 cutaneous SCC was analyzed for survivin expression by immunohistochemistry and Western blotting. Survivin was found in 57 cases (64%) of skin SCC and 26 cases (56%) of oral SCC, with weighted survivin scores ranging from 1 to 12. In contrast, normal oral epithelium, normal skin epithelium, and skin annexa did not express survivin. Survivin expression significantly (P < 0.05) segregated with high-grade and undifferentiated tumors with size >1.5 cm and invariably associated with lymph node metastasis. These data suggest that survivin expression may predictively identify cases of SCC with more aggressive and invasive clinical phenotype, potentially warranting closer follow-up protocols.
Abstract: A comparative study of 96 Spline and Threadloc implants is presented. The authors examined the possibility of the failure of the retaining screws of two different antirotational systems (the Threadloc system with hexagonal polyhedral extension and the Spline system), and the possible incorrect link between the abutment and the transfer. After an observation period of 36 months starting from the day of prosthesis insertion, three single Threadloc fixtures (20%) and five pairs of joint Threadloc fixtures (5.7%) presented problems and a partial prosthetic screw loosening. For the Spline series fixtures, no screw loosening was encountered. Regarding the safety of the link between abutment and implant, the best results were obtained from the Spline system, which did not hinder the dentist in positioning the link with the abutment. This is the result of the different geometries of the two antirotational mechanisms which are present on the two fixtures. It is believed that the precise contact between the abutment and the fixture avoids the triggering of a phlogistic process, which can develop into periimplantitis. Therefore, when hex systems are used, an x-ray, which verifies this correct situation, is always recommended during the follow-up.
Abstract: BACKGROUND, AIMS: Orofacial granulomatosis (OFG) is a descriptive term used for granulomatous disorders of the face and oral cavity that may occur for a variety of reasons, some of which result in significant morbidity and mortality. Although rarely, a granular enlargements of the gingiva may be the first clinical manifestation of OFG, preceding other local or systemic manifestations. METHOD: We will report a case of OFG that showed an atypical and monosymptomatic onset with a generalized hyperplastic gingivitis that preceded other facial and mucosal features by several weeks. RESULT: Considering the variable clinical onset of OFG and its apparent increase in incidence, we emphasize that in some cases, the periodontologist, as first consulted health care professional, plays an important role to detect this disorder. Early diagnosis of OFG is a crucial step to prevent and cure its unsightly sequelae and sometimes avoid progression of systemic potentially life-threatening OFG-related diseases. CONCLUSION: Thus, when none of the common causes of gingival enlargement can be detected, OFG diagnosis should be suspected.
Abstract: Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease for all cancers. Proteins involved in intercellular adhesion, such as E-cadherin and catenin, probably play an important role in metastatic processes and cellular differentiation. While E-cadherin and beta-catenin expression has been extensively studied in many forms of human cancers, less is known about the role of the Wingless-Type-1 (WNT-1) pathway in human tumors. A large body of genetic and biochemical evidence has identified beta-catenin as a key downstream component of the WNT signaling pathway, and recent studies of colorectal tumors have shown a functional link among beta-catenin, adenomatous polyposis coli gene product (APC), and other components of the WNT-1 pathway. WNT-1 pathway signaling is thought to be mediated via interactions between beta-catenin and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and promotes its accumulation in the cytoplasm and nucleus. In the nucleus, beta-catenin associates with TCF to form a functional transcription factor which mediates the transactivation of target genes involved in the promotion of tumor progression, invasion, and metastasis, such as C-Myc, cyclin D1, c-jun, fra-1, and u-PAR. There is a strong correlation between the ability of the WNT-1 gene to induce beta-catenin accumulation and its transforming potential in vivo, suggesting that the WNT-1 gene activates an intracellular signaling pathway that can induce the morphological transformation of cells. For these reasons, data obtained from the study of the WNT-1 pathway could be important in our understanding of the mechanisms of epithelial tumors, in general, and probably also of oral squamous cell carcinoma, in particular.
Abstract: In recent years, studies on the malignant potential of oral lichen planus (OLP) provided clinical evidence that patients affected by OLP have an increased risk to develop oral squamous cell carcinoma (OSCC); nevertheless, controversies still exist as to whether OLP has inherent predisposition to become malignant, or not. We believe extremely careful management of OLP patient is mandatory, and the aim of this paper is to illustrate our clinical guidelines in evaluating the possible risk of transformation in OLP lesions. Five-hundred and two patients (311 women and 191 men) affected by OLP regularly undergo follow-up examination in our Department. Patients' ages range from 18 to 83 years, with a mean of 55.4 years (57.5 for women and 53.9 for men); minimal follow-up period is 4 months, with a maximum of 12 years. In our group of OLP patients in the past 5 years we detected 24 carcinomas: excluding three cases in which diagnoses of OLP and OSCC were synchronous and three patients who had a history of tobacco use, thus possible malignant transformation of OLP would appear to be 3.7%. Clinical criteria used in our follow-up allowed us to detect 28.5% of tumours as in situ OSCC, 38% as microinvasive OSCC, 28.5% as stage I OSCC and 4.7% as stage II OSCC, with a remarkable improvement in prognosis compared to our previous study in which we adopted different criteria.
Abstract: Cell-to-cell adhesion is mediated by cadherins (integral membrane proteins), which form a complex with catenins (cytoplasmatic proteins). While E-cadherin expression has been extensively studied in many human skin diseases, less is known about the expression levels of catenins in oral blistering diseases. The purpose of this study was to evaluate the role of these proteins in the pathogenesis of acantholysis in oral pemphigus vulgaris. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 7 cases of oral pemphigus vulgaris (PV) at various stages of the disease and, as controls, in 18 healthy patients. Healthy cases showed, as reported in the literature, a strong reactivity with both beta- and gamma-catenins, with the intensity of staining progressively decreasing from the spinous to the keratinised layers of epithelium, which had a prevalent cellular membrane expression. In PV patients, we detected a loss of membrane expression of these molecules with a progressive displacement of the signal toward the cytosol and, for gamma-catenin, nuclear dislocation, particularly in areas with intense acantholysis.
Abstract: BACKGROUND: Pemphigus vulgaris (PV) is a rare, chronic, intraepithelial bullous disease with a potentially fatal outcome. Oral lesions are a hallmark of PV and occur in almost all cases, and represent the preliminary symptom in more than half of the patients. Gingival lesions are very common and, when solitary, often first recognized by periodontist. METHOD: In the literature, gingival localization of PV are usually described as desquamative gingivitis (DG) and/or as vesiculobullous lesions of the free and attached gingiva; in our experience, early lesions only rarely appears as extensive erythema and erosions. CONCLUSIONS: PV at the onset may frequently appear on gingiva as isolated blisters and/or erosions mainly located to the free gingiva, very little in extension and hardly to recognize as bullous lesions.
Abstract: Basal cell carcinomas (BCCs) may be subdivided into primary with a favorable biologic course (BCC1) and recurrent and/or metastatic (BCC2). No clear association between primary tumor location, histologic subtype, or other clinicopathologic variables and predisposition for BCC2 has been found. Histopathologic criteria are limited for prognostication. To identify prognostic factors useful for planning therapy, we studied cyclin D1 immunohistochemical expression, DNA ploidy, and epiluminescence light microscopic (ELM) patterns in 60 cases of BCC (30 BCC1 and 30 BCC2) in the head and neck region, half of which were hyperpigmented. Cyclin D1 was absent in 27 cases, expressed at low level in 4 cases, and overexpressed in 30 cases. Seven BCCs were euploid, 28 exhibited a mixed cellular population, and 25 were aneuploid. Among aneuploid tumors, hypodiploidy was found in 12. Among the 30 pigmented carcinomas, only 15 showed a typical ELM pattern. No association between pigmentation and more aggressive biologic behavior of BCC was found. These results and follow-up data seem to indicate that an unfavorable outcome can be predicted by hyperexpression of cyclin D1, aneuploidy, and an atypical ELM pattern for pigmented cases. A definite hypodiploid peak was associated with worse prognosis. The analysis of cyclin D1 expression and DNA ploidy may help identify BCC with an aggressive phenotype and a poor clinical outcome.
Abstract: The authors reported a case of a solitary mandibular plasmacytoma in a 53-year-old male Caucasian patient. The histological examination of the specimen was positive for a plasmacytoma with anaplastic appearance. Since the patient refused a demolitive surgical treatment, he was treated with a local radiation therapy of 4000 rads over a 20-day period and polychemotherapy with cyclophosphamide, prednisone and melphalan. Six years after starting radiation treatment the patient is free of recurrent primary disease and not affected by multiple localization. In conclusion, the solitary bone plasmacytoma represents an initial stage of the multiple myeloma rather than a distinct clinical pathology. Unfortunately, the diagnosis of the plasmacytoma is only rarely carried out in the early phases of the disease. The importance of the identification of the initial stage without a clear M component, as in the reported case, is self-evident, since the prognosis is related to the mass of plasmacytoma cells that are present at the time of the diagnosis. The purpose of this study is to report an extremely rare case of solitary bone plasmacytoma with a mandibular localization treated with radio- and polychemotherapy.
Abstract: Integrins are transmembrane receptors that regulate cell-cell and cell-extracellular matrix (ECM) contact. In epithelial tissues, they interact with ECM components of the basement membrane (BM) to maintain the homeostasis and the architecture of the tissue. This interaction controls several cell functions such as adhesion, migration, proliferation, differentiation, and therefore has a key role in cancer development and metastasis. We studied the expression of integrins and ECM components of the BM by immunohistochemistry in frozen specimens of malignant squamous cell carcinoma (SCC), pre-malignant lesions of the oral mucosa (leucoplakia) and oral lichen planus. In invasive SCC, we observed altered polarity and distribution of alpha2beta1, alpha6beta4 and alpha3beta1 integrins, whereas in the in situ carcinoma alpha6beta4 and alpha3beta1 patterns only were altered. Immunostaining for ECM components such as Laminin-1 (Ln-1), Ln-5, and Collagen IV (Coll IV) was discontinuous and interrupted in invasive SCC, whereas it was normal in the in situ carcinoma. In both pre-malignant lesions and lichen planus specimens, integrins were expressed in a polarized manner in the presence of a normal BM, whereas were abnormally distributed in those tissues with altered staining patterns of the ECM components. In conclusion, we suggest that abnormal re-distribution of alpha3beta1 and alpha6beta4 integrins and expression of ECM components such as Ln-5 could play an important role in SCC invasion and metastasis.
Abstract: BACKGROUND: Basal cell carcinoma (BCC) is the most frequent tumor of the human skin and generally shows a favourable clinical behaviour. However, a percentage of BCC grows aggressively, infiltrating contiguous structures, sometimes giving distant metastases. MATERIALS AND METHODS: Bcl-2 and p53 protein expression was studied immunohistochemically in 60 cases of BCC (30 non-aggressive, BCC1 and 30 aggressive cases, BCC2) of the head and neck region with a complete clinical follow-up. RESULTS: All the BCC1 showed distinct cytoplasmic staining for bcl-2. The intensity of staining ranged from intermediate to high, with only three cases showing low positivity. Among BCC2, none of the 30 cases showed positivity for bcl-2. Bcl-2 expression was directly correlated with the BCC1 sub-type and a favourable clinical follow-up (p<0.01). Among BCC1, 27 cases were found negative for p53 protein expression while 3 exhibited only a low immunoreactivity. Among BCC2, 11 out of 30 cases showed an intermediate immunoreactivity, and 18 out of 30 exhibited high positivity for p53 protein. The expression of p53 protein correlated inversely with cellular differentiation (p<0.01). CONCLUSION: From the analysis of these results it is reasonable to consider bcl-2 and p53 protein expression as useful discriminating prognostic factors in the evaluation of BCCs of the head and neck region. In fact, the finding of clones expressing bcl-2 in a case of BCC may be indicative of an "indolent" cellular neoplastic phenotype. In other words, bcl-2 could be used as a "clonal marker" of a still favourable clinical behaviour. Conversely, the partial or complete loss of bcl-2-bearing neoplastic clones during histological transformation, with the appearance of clones expressing p53 protein in a BCC could be considered a hallmark of transition from a low-to high-grade malignancy, characterized by the emergence of cellular clones with a more aggressive phenotype, responsible for worse clinical behaviour.
Abstract: Ultraviolet (UV) radiation plays a pivotal role in skin damage and photocarcinogenesis. The basic mechanism of phototoxicity lies in DNA damage, and involves mutation of tumor suppressor genes, oncogenes and genes directly involved in the control of the stability of genome, such as the mismatch repair (MR) genes. The goal of this study was to evaluate the role of p53 and hMSH2 in the UV-related carcinogenetic process. An immunohistochemical study for p53 and hMSH2 was performed in a series of 43 basal cell carcinomas (BCC) and 60 melanomas (MM) from photoexposed areas of head and neck region, comparing the findings with follow-up. A deregulated p53 expression characterized less differentiated, more aggressive BCC (BCC2) but not the well-differentiated ones (BCC1). The hMSH2 protein was present, though expressed at varying levels, in 18 out of 21 BCC1 cases and in 4 out of 22 BCC2. In the remaining 3 cases of BCC1 and 18 cases of BCC2, a complete absence of hMSH2 expression was found, correlating directly with the presence of recurrence and/or death of the disease in case of melanoma (p<0.05). Overall, the expression of hMSH2 correlated inversely with the p53 overexpression (p<0.01). In MM, p53 was found overexpressed in 81.6% of the cases, and this correlated positively with the level of infiltration and with the presence of relapses (p<0.01) or metastasis (p<0.01) and inversely with the disease-free interval (p<0.05). These results are in agreement with the reported association between p53 deregulation and a more aggressive cancer phenotype. The evaluation of the expression of p53 and hMSH2 could improve the management of patients with BCC and MM, and could have a role also in the evaluation of the early cutaneous photo-inducted damage, contributing to the identification of presymptomatic patients predisposed to the development of UV-related new skin tumors, who could become candidates for chemoprevention trials.
Abstract: Oral lichen planus (OLP) is classified among precancerous conditions, as it is considered a generalized state associated with a significantly increased risk of cancer. The objective of this study was to discuss ultra-structural aspects of OLP that could play a role in enhancing metastatic potential, thus worsening the prognosis in oral squamous-cell carcinoma (OSCC). We report four cases of microinvasive OSCC which have occurred in OLP patients. All of them were stage I tumors, with a mean thickness of 1.75 mm. Recent studies indicate a tumor thickness over 4 mm as predictive of nodal metastases, but within 6 mo, our four patients with OSCC arising from OLP developed lymphnodal metastases. Our findings suggest that OLP-related OSCC may have a worse prognosis because of increased metastatic potential; obviously, further investigation is required, but this preliminary evidence emphasizes that extremely careful management of OLP patients is mandatory, and in cases of OSCC arising from OLP, a more radical treatment is probably required.
Abstract: BACKGROUND: This study evaluated the clinical use of a corticosteroid in three preparations (topical clobetasol propionate ointment, clobetasol propionate in an oral analgesic base, and clobetasol propionate in an adhesive denture paste). METHODS: Fifty-four patients (34 males and 20 females) with a history of vesiculo-ulcero-erosive oral lesions were selected: 24 with oral erosive lichen planus and 30 with aphthae. The subjects enrolled were randomly divided into three groups, each of 18 patients (10 with aphthae and 8 with lichen planus): the first was treated with topical clobetasol propionate ointment (0.05%) directly on the lesion(s) three times a day; the second with clobetasol propionate in an adhesive denture paste in equal amounts (1:1) two times a day; the third with clobetasol propionate in an oral analgesic base (Orabase-B) in equal amounts (1:1) two times a day. Each subject scored his or her symptoms daily from most severe (7) to none (0) by verbal assessments using a categorical scale. RESULTS: In all cases, the administration of the corticosteroid was effective in producing remission of symptoms in each group of patients. Significant differences (P<0.05) between groups were determined by the Kruskal-Wallis test. The Dunn test was used in order to detect which group differs from the others; clobetasol and adhesive denture paste correlated with an early remission of pain in lichen and apthous lesions. CONCLUSION: The results suggest that topical application of clobetasol in an adhesive denture paste is an effective drug for symptomatic oral vesiculo-erosive and/or ulcerative lesions.
Abstract: BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of beta- and gamma-catenins in blistering diseases. The objective of this study was to evaluate the role of beta- and gamma-catenins in the pathogenesis of acantholysis in pemphigus vulgaris. METHODS: beta- and gamma-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients. RESULTS: Healthy skin and normal oral mucosa showed a strong beta- and gamma-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of gamma-catenin was detected in 28/30 cases, and in 19/30 cases of PV for beta-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for beta-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for gamma-catenin. CONCLUSIONS: Abnormal distribution of gamma-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. gamma-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the beta-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.
Abstract: A case of primary intraosseous carcinoma of the mandible in a 75-year-old man is reported. This tumor is an uncommon lesion arising from odontogenic rests. This tumor affects men more than women and is more frequent in the sixth and seventh decades of age. Most tumors occur in the posterior mandible as painful, non-ulcerated lesions, even if several cases have shown complete absence of subjective symptoms in early phases; often they are detected first on routine radiographs. Radiographically the lesion usually shows a fully enclosed, irregular pattern of bone destruction, even if sometimes the margins are well defined. The accepted treatment is radical surgery; but metastases could occur in lymph nodes.
Abstract: BACKGROUND: Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. OBJECTIVE: To determine whether differences exist in the clinical features and behavior of oral lichen planus (OLP) between HCV-positive (HCV+ve) and HCV-negative (HCV-ve) patients. METHODS: Two hundred and sixty three patients (156 women and 107 men), with a mean age of 55.5 years, with OLP (76 HCV+ve and 187 HCV-ve) were clinically evaluated. Previously, all local factors that could modify the clinical characteristics were removed and were monitored carefully following morphology. RESULTS: In both groups, the prevalent clinical form of OLP was the mixed form (33.1% in HCV-ve and 35.5% in HCV+ve patients), in which reticular-plaque lesions coexist with atrophic-erosive ones. The reticular form was more frequent in HCV+ve (25%) than in HCV-ve (18. 7%) patients, whereas plaque lesions were more prevalent in HCV-ve (15.5%) than in HCV+ve (5.2%) patients (P < 0.01, chi-squared test). There were no significant differences in the frequency of erosive (27.2% in HCV-ve and 27.6% in HCV+ve) and atrophic (5.3% in HCV-ve and 5.2% in HCV+ve) forms between the two groups. CONCLUSIONS: Our findings show that there were statistically significant differences between OLP-HCV-ve and OLP-HCV+ve groups for reticular and plaque clinical forms. These findings underline the importance of liver examination in all OLP patients, including cases with mild, asymptomatic keratotic forms of the disease.
Abstract: BACKGROUND: The DNA mismatch repair system (MMR) plays an important role in the maintenance of genomic stability. To date few studies have been performed on hMSH2 and hMLH1 expression and melanoma of the head and neck region. A study of two cases revealed no mutations of the mismatch repair genes hMSH2 and hMLH1. MATERIALS AND METHODS: To verify the possibility of implication of hMSH2 and hMLH1 alterations in melanocytic cancerogenesis, the authors examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in 9 paraffin-embedded oral melanoma. RESULTS: One case (11%) showed nuclear positivity for hMSH2, 3 cases (33%) showed cytoplasmic positivity, and five cases (55%) showed no staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Four cases (44%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity. Two cases (22%) showed nuclear positivity, and three cases (33%) showed cytoplasmic positivity. CONCLUSIONS: The analysis of mismatch repair genes can be a new molecular diagnostic tools for the detection of patients at high risk of developing melanoma and other neoplasia, or metastasis and recurrences.
Abstract: Systemic corticosteroids remain the mainstay of therapy for pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. Unfortunately, the high doses and prolonged administration of corticosteroids that are often needed to control the disease result in numerous side effects, many of which are serious or even life-threatening. Sixteen patients affected by oral pemphigus vulgaris were retrospectively examined to illustrate the natural course of the disease and to describe the efficacy of the treatment we utilised. Deflazacort, used with azathioprine, is the steroid of first choice in our therapeutic protocols, while cyclophosphamide and methylprednisolone "pulse therapy" are reserved for cases unresponsive to high doses of oral corticosteroids. In addition, the literature on oral pemphigus vulgaris was reviewed with respect to clinical history, signs and symptoms, management, and treatment outcome.
Abstract: PURPOSE: Non-Hodgkin's lymphoma (NHL) comprises a group of malignant lymphoproliferative diseases characterized by clonal expansion of lymphocytes at various levels of ontogenetic development. The aim of this study was to review the immunohistochemical and cytogenetic features of 10 cases of NLH of the jaws to determine their respective derivation. PATIENTS AND METHODS: Histopathologic and immunohistochemical review of 10 cases of large-cell lymphomas of the jaws, together with Southern blot analysis of 2 of the cases, was performed and results compared with the findings in the literature. RESULTS: In the 10 cases studied, the average age of onset of the NHL was 51 years, with a male-to-female ratio of 3:2. Tumefaction was the first clinical sign of disease. Eight of 10 cases were high-grade, large-cell NHLs, centroblastic type. Two cases were high-grade, large-cell NHL, immunoblastic type. CONCLUSION: The immunohistochemical and Southern blot data remain the principal laboratory aids in the diagnosis and characterization of NHL, and they provide critical information for guiding clinicians to the appropriate treatment protocol for these malignancies.
Abstract: A large number of oral cancer patients show poor or partial response to chemotherapy and the mechanisms are poorly understood. At present, an MDR-1 product, the P-170 glycoprotein, is the best known of the P-170 family and is involved in resistance to natural product-based chemotherapeutics, including taxanes, anthracyclines, vinca alkaloids, podophyllotoxins and camptothecins. Although several reports suggest that P-170 is clinically relevant in haematological malignancies, its role in solid tumours is not well understood. Its overexpression has been found to be correlated with the poor outcome observed in patients treated with chemotherapy and presenting drug resistance. The aim of this study was to detect the protein expression patterns of MDR-1 product by immunohistochemistry in formalin-fixed-paraffin-embedded tissues. For these reasons, 30 oral SCC and 6 healthy oral mucosa specimens were tested with anti-P-170 antibodies using standard streptavidin-biotin-peroxide technique. Immunohistochemistry demonstrated that 4 cases (66.6%) of normal oral mucosa and 24 cases (80%) of oral SCC showed positivity. Four cases (13.4%) showed strong positivity in tumour areas and complete negativity in normal epithelial cells adjacent to the tumour. No staining was observed in stromal structures, with the exception of the lymphocytic compartment that showed a strong staining as reported in literature for CD56+ and CD8+ cells. Four G1 tumours (33%) and 2 G3 tumour (33%) showed strong positivity in areas with a higher degree of differentiation. P-170 positivity in normal epithelial cells of smoker patients, in differentiated area of neoplasia and negativity or zonal positivity in undifferentiated area of tumour suggested that activation of the MDR-1 gene or selection of intrinsically multidrug resistance neoplastic cells may occur at early stages of tumorigenesis of oral cancers, before the real evidence of cellular transformation. Thus the contact with possible chemical carcinogens, such as those of tobacco smoke, may induce activation of MDR-1 gene. This study was conducted only on untreated carcinomas so for this reason it cannot indicate the real incidence of acquired multidrug resistance. The data of MDR-1 product expression by immunohistochemistry in oral SCC might suggest that an overexpression of this protein could constitute a hallmark of potential more aggressive phenotype for this type of neoplasia and a rapid method for pre-screening tumours for a constitutive multidrug resistance in order to orientate the cancer treatment.
Abstract: Leiomyosarcoma is a relatively uncommon mesenchymal tumor that exhibits smooth-muscle differentiation. We report a new case of leiomyosarcoma involving the tongue of a 67-year-old male. Histologically, the tumor was composed of variably oriented fascicles of spindle-shaped cells with 'cigar-shaped' nuclei and eosinophilic cytoplasm, containing occasional PAS-positive granules. Atypical mitotic figures and necrotic foci were frequently detected. Consistent desmin, alpha-smooth muscle-specific and sarcomeric actin, and vimentin immunoreactivity was demonstrated in the tumor cells, whereas cytokeratins, CD 30, CD 31, CD 34, CD 45, CD 68, EMA, GFAP, HMB 45 and S-100 protein were negative. The patient underwent wide surgical excision of the tumor and is alive and disease-free at a 5-year follow-up. This report emphasizes the difficulties in the differential diagnosis of these uncommon tumors in an intra-oral location.
Abstract: BACKGROUND: Nevoid basal cell carcinoma syndrome, or NBCCS, is a hereditary condition characterized by basal cell carcinomas, or BCCs; odontogenic keratocysts, or OKCs; and skeletal abnormalities. The authors conducted this study to determine the early signs of NBCCS. METHODS: The authors reviewed files from two Italian dental schools from January 1980 to January 1995 to determine the early signs of NBCCS and the age at which patients were first examined. They re-examined all of the patients, using the diagnostic criteria for NBCCS. RESULTS: The authors found 14 patients who fulfilled the criteria for diagnosis of NBCCS in five families. All of the patients were 16 years of age or younger. In 11 cases (78 percent), the first sign of NBCCS in the patients was an OKC. The OKCs diagnosed in patients older than 13 years of age were large and characterized by widespread bone resorption. One 11-year-old patient had six large OKCs. The authors also found a case of multiple OKCs in an 8-year-old patient. Only one patient showed BCCs. CONCLUSIONS: OKCs are often the first signs of NBCCS and can be detected in patients younger than 10 years of age. Our data suggest that OKCs arise earlier in patients who have NBCCS than in patients who do not have NBCCS. The patients' young ages explain the low incidence of BCCs in this study. CLINICAL IMPLICATIONS: The presence of multiple OKCs in a child or onset of BCC in a patient younger than 20 years of age should alert dentists to the possibility of the patient's having NBCCS.
Abstract: OBJECTIVE: To present a clinical, histopathological and ultrastructural study on a group of patients affected by idiopathic mucocutaneous pigmentation (Laugier-Hunziker syndrome: LHS). MATERIALS AND METHODS: Twelve patients were investigated: clinical examination, laboratory tests, and X-ray studies together with light microscopy and electron microscopy were performed in order to diagnose LHS. RESULTS: All cases showed acquired, benign, macular hyperpigmentation of buccal mucosa lips and nails. Histologically, pigmentations are due to an accumulation of melanin in the basal layer keratinocytes and an increase in the number of melanophages in the submucosa and/or papillary dermis. Ultrastructurally there were increased numbers of normal-appearing melanosomes in keratinocytes of the lower epithelium. No evidence of malignant changes were detected. CONCLUSIONS: The importance of this condition relates to it being included in the differential diagnoses of pigmentary disorders of the oral mucosa with associated nail involvement. It is important to recognize this acquired benign disorder to avoid unnecessary investigations and treatments.
Abstract: Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary condition transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. The syndrome is characterised by numerous basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, palmar and/or plantar pits, skeletal abnormalities and intracranial calcifications. In this paper, the clinical features of 37 Italian patients are reviewed. Jaw cysts and calcification of falx cerebri were the most frequently observed anomalies, followed by BCCs and palmar/plantar pits. Similar to the case of African Americans, the relatively low frequency of BCCs in the Italian population is probably due to protective skin pigmentation. A future search based on mutation screening might establish a possible genotype phenotype correlation in Italian patients.
Abstract: BACKGROUND: The loss of DNA mismatch repair system was reported in hereditary non-poliposis colon cancer and in other tumours. The aim of this study was to detect the protein expression pattern of hMSH2 and hMLH1 in oral squamous cell carcinoma (SCC) by immunohistochemistry in paraffin-embedded tissues. MATERIALS AND METHODS: 5 specimens, obtained from healthy oral mucosa, and 20 from oral SCC were tested with anti-hMSH2 and anti-hMLH1 monoclonal antibodies. RESULTS: Six cases (30%) showed nuclear positivity in differentiated areas (G1) and cytoplasmic positivity in areas with a lower degree of differentiation, four cases (20%) showed only cytoplasmic positivity, and only one (5%) no staining. One case of oral SCC (5%) showed no hMLH1 staining in the tumoral cells, even if normal squamous epithelium available in this section showed a nuclear positivity; six cases (30%) showed nuclear positivity in differentiated areas (G1) and cytoplasmic positivity in areas with a lower degree of differentiation, three cases (15%) showed only cytoplasmic positivity. CONCLUSIONS: These data suggest that examination of hMSH2 and hMLH1 protein expression by immunohistochemistry is important in oral SCC. The analysis of mismatches expression in these cases of oral SCC might suggest that an absent nuclear staining for both hMSH2 and hML1 could constitute a hallmark of potential phenotype mutator for this type of neoplasia.
Abstract: The murine nm23, a putative metastasis suppressor, has three human homologues, NM23-H1, -H2, and -H3b. Several reports have suggested a low metastatic potential for neoplasms with a high expression of NM23-H1 gene, while other studies have not shown this relationship. These apparent differences in the role of NM23 in metastasis suppression might be explained by unability to discriminate between the expression of the two genes NM23-H1 and NM23-H2. The NM23-H2 product is not related to tumor progression and metastasis suppression. Two studies on human oral squamous cell carcinoma (OSCC) have been reported, both showing the NM23 product to be a metastasis suppressor factor. However, none of these two studies distinguished NM23-H1 from NM23-H2. The aim of this study was to detect the protein expression pattern of NM23-H1 product in 24 OSCCs by immunohistochemistry in paraffin-embedded tissues using a monoclonal antibody non-cross-reactive with NM23-H2. The NM23-H1 positive group showed lower frequency of lymph node metastasis, and a better grading than the NM23-H1 negative group supporting the role of NM23-H1 as metastasis suppressor factor which may be useful for predicting tumor metastasis in OSCC.
Abstract: Basal cell carcinoma (BCC) is the most common type of human cancer, often locally invasive, and following a benign clinical course. However, a proportion of BCCs do recur after treatment, causing extensive local tissue destruction, seldom metastasizing. Morphological methods to unequivocally distinguish the aggressive forms of these tumors (BCC2) from the ordinary ones (BCC1) have so far been lacking. Apoptosis, or programmed cell death, is thought to be important for the death of tumor cells in various stages of carcinogenesis. We analyzed the extent of apoptosis in BCCs of head and neck in a morphological, morphometric, and electron-microscopic study, to estabilish on a retrospective basis, the relative frequency of recurrence of tumors showing different apoptotic rates. We found that BCC1 showed lower apoptotic index (AI) than BCC2 [BCC1: AI from 2.03 to 10.45% (mean value: 5.98%) BCC2: AI from 21. 91 up to 43.82% (mean value: 39.82%)]. The morphometric analysis of both BCC1 and BCC2 revealed significant differences between the values concerning nuclear area, length, perimeter, and roundness of the apoptotic cells with respect to the 'viable' neoplastic cells. Electron-microscopy confirmed that the features of morphological apoptotic cells were characteristic of programmed cell death. We hypothesized that low apoptotic rates in BCC1 could be indicative of a good prognosis. In fact, this corresponded to an 'expansive' but not still invasive neoplastic state. In this phase, however, the tumor cells may constitute the target for genetic changes triggered by enviromental physical or chemical mutagenic agents, such as UV rays. BCC2, then, could be the result of newly selected mutated neoplastic cellular clones, with more aggressive biological behavior. The high apoptotic level found in BCC2 could thus be used as an indirect alarm signal from pathologists. This hypothesis seems to be supported by most of the current data in the literature and by the clinical outcome of BCC2 of our series. In our opinion, routine evaluation of apoptosis in BCCs could be proposed to facilitate their sub-classification, contributing toward the evaluation of the prospective outcome of the individual patients.
Abstract: The cellular changes leading to carcinoma of the lip are still not completely understood. This study was carried out on 44 malignant and potentially malignant lesions of the lower lip [30 squamous cell carcinomas (SCC), 7 actinic cheilitis, 3 leukoplakias, and 4 nodal metastases from lower lip SCC]. Silver-stained nucleolar organizer regions (AgNORs) and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA), p53, and c-myc were evaluated on formalin-fixed, paraffin-embedded sections. The results indicate that the size and numbers of AgNORs and the percentage of PCNA-positive cells are sensitive parameters for discriminating between potentially malignant lesions and SCC, and for the prognostic sub-typing of lower lip SCC. Furthermore, while p53 positivity was found more frequently in high-grade carcinomas, p53-positive cellular clones were also found in some potentially malignant lesions, a finding probably related to ultraviolet-related cellular damage. These p53-positive lesions could be considered at higher risk of progression to malignancy than the p53-negative ones, although there is no evidence for this as yet. c-myc positivity was found only in some high-grade carcinomas and metastases, and appeared correlated with the later phases of lip carcinogenesis. The combined evaluation of the proliferation status, together with the changes in p53 and c-myc oncoproteins, might constitute useful markers for the prognostic evaluation of potentially malignant, as well as malignant, lesions of the lip.
Abstract: Cell-cell adhesion is mediated by cadherins (integral membrane proteins) which form a complex with catenins (cytoplasmatic proteins). Down-regulation of cadherins and more recently of catenins has frequently been detected in many types of human carcinomas, in which it has been associated to tumor progression. While E-cadherin expression has been extensively studied in many forms of human cancers, including oral SCC, less is known about the expression levels of catenins in oral SCCs. The objective of this study was to evaluate the role of these proteins in the carcinogenetic process of the oral cavity. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 30 cases of intraoral squamous cell carcinomas at different degree of cellular differentiation. As already reported for E-cadherin, the beta- and gamma-catenin expression showed an inverse relationship with the degree of differentiation, being the membranous expression of both catenins homogeneously reduced in less differentiated oral squamous cell carcinomas (grade 3). More interestingly, a decreased expression of these molecules was also found at the invasive front of grade 2 and sometimes of grade 1 carcinomas, thus suggesting a more aggressive biological behavior of these cancer cells. An absent staining for both beta- and gamma-catenins could constitute a hallmark of aggressive biological behavior even in tumor still well or moderately differentiated, at least in the peripheral invading front constituted by less differentiated tumor cells.
Abstract: Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the development of different neoplasms. The aim of this study was to establish whether keratocysts showing clinically aggressive behavior associated with nevoid basal cell carcinoma syndrome reflect differences in cellular proliferation rate and/or in the expression of oncoproteins and tumor suppressor genes. For this reason, formalin-fixed paraffin-embedded sections of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) onco-proteins. Most of the epithelial lining of odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome showed nuclear immunopositivity for p53 protein and overexpression of cyclin D1 with various degrees of staining intensity. All sporadic odontogenic keratocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncoprotein were found to be substantially similar between the two groups of lesions, with a cytoplasmic immunopositivity localized only in the resting reserve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, the finding of cyclin D1 and p53 overexpression in odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point control of cellular proliferation.
Abstract: BACKGROUND: Hepatitis C virus (HCV) infection induces variable dermatologic manifestations. Our purpose was to determine whether there is an association between HCV infection and oral lichen planus (OLP). METHODS: Antibodies to HCV were determined in patients with OLP (263 patients; 156 women and 107 men, with a mean age of 55.5 years) and in a control population. RESULTS: Seventy six cases (28.8%) were positive for HCV antibodies with the second-generation enzyme-linked immunosorbent assay (ELISA II) test. All of these cases were confirmed with the second-generation recombinant immunoblot assay (RIBA II) test. In 61 cases (23.1%), high levels of serum transaminase were found. Positivity for hepatitis B virus (HBV) markers was found in 31 patients (11.7%) and for hepatitis A virus (HAV) markers in 43 patients (16.3%). None had positivity for hepatitis D virus (HDV) markers. As a control group, we used 100 patients (58 women and 42 men, with a mean age of 55.3 years) referred to the School of Dentistry of the University of Naples "Federico II," and treated for general dental caries. In the control group, HCV antibody positivity was found in three cases. CONCLUSIONS: The high prevalence of HCV antibody in this group of patients with OLP, higher than in the healthy population, suggests a link (p = 1.423 x 10(-7), chi-squared test) between these two diseases. These findings stress the importance of liver examination in OLP patients, and the need for other studies on the high susceptibility to hepatitis viruses in the population in the southern part of Europe.
Abstract: MATERIALS AND METHODS: Ten human healthy teeth were extracted for orthodontic or surgical purposes and processed for histological and immunocytochemical examination with the streptavidin-biotin-peroxidase method. Highly purified antibodies were used to reveal the distribution of intermediate filaments (vimentin, desmin, alpha-smooth muscle actin), histiocytic antigens (alpha-1-antitrypsin, lysozyme), neural and neural-crest-associated antigens (neuron-specific enolase, chromogranin-A, S-100, synaptophysin, glial fibrillary acidic protein, neurofilaments) in the adult pulp tissue. RESULTS: Vimentin immunostaining was strongly positive in the network of pulpal fibroblasts. Desmin and alpha-smooth muscle actin were present only in the vessel walls. Staining for alpha-1-antitrypsin and lysozyme reveals a number of macrophage-like cells in the central portion of the pulp. Macrophages were the most dominating immunocompetent cells. Negative immunostaining for chromogranin-A demonstrated the absence of neuroendocrine antigens in the adult dental pulp. Immunostaining for neuron-specific enolase, S-100 protein, synaptophysin, glial fibrillary acidic protein and neurofilaments were positive, with different intensity, in nerve fibres, but no pulp cell was found to be immunoreactive. CONCLUSIONS. The conclusion is drawn that the lack of labelling of pulp cells by the neural associated antibodies could be due to differentiation processes during tissue development.
Abstract: Cowden disease (CD) is an autosomal dominant multiple hamartoma syndrome with an elevated risk of thyroid and breast cancers. The CD susceptibility gene has recently been identified as the PTEN/MMAC1/TEP1 gene localized at 10q23 and coding for a dual specificity protein phosphatase. We report the mutational analysis of the PTEN gene in one Italian CD kindred. By using the single strand conformation polymorphism technique and subsequent direct DNA sequencing of the polymerase chain reaction product, we identified a novel mutation in the exon 5 of the PTEN gene. A heterozygous germline TGT-TAT transition was detected at the nucleotide 407; this causes the amino acid substitution cys136-tyr136 and the generation of a new NSI I restriction site. This mutation was not detected in the unaffected member of the family thereby indicating that it is causally linked to the disease. We ruled out that this mutation is a polymorphic variant because it was not detected in over 100 chromosomes analyzed. Using reverse trancriptase-polymerase chain reaction, we detected the expression of the mutant allele in lymphocytes and pathological tissues from an affected member of the family.
Abstract: BACKGROUND: Catenins belong to a family of proteins that mediate the binding between intracytoplasmic domain of cadherins and cytoskeleton. Few data on distribution of beta and gamma catenins in non-neoplastic tissues are available from current literature. This study aims to evaluate distribution of beta and gamma catenins in oral epithelium. METHODS: Nine formalin-fixed and paraffin-embedded samples of oral epithelium were retrieved from files of Department of Oral Pathology of the University of Naples "Federico II". These samples were tested with anti-beta and anti-gamma monoclonal antibodies revealed by standard streptavidin-biotin-peroxidase technique. Sections have been evaluated by two observers by optical microscope using a 40X objective. The number of positive cells has been evaluated using a semi-quantitative method. RESULTS: The results of this study show that beta and gamma catenins were mostly distributed in the upper two-thirds of oral epithelial thickness, except for keratinized areas which appear negative. Basal layer is positive except for the basal side of basal cells. Keratinized layers are negative for beta and gamma catenins. CONCLUSIONS: In physiologic conditions staining pattern for beta and gamma catenins is almost exclusively membranous, sometimes cytoplasmic but never nuclear. This staining is well-represented even in conditions of chronic inflammation and leucoplakia.
Abstract: BACKGROUND: It is known that tumoral progression towards a metastatic stage is identifiable with a genomic instability. This instability leads to both primary and secondary genetic alterations. It can give some selective proliferative advantages. This study aims to review the literature on instability of the microsatellite sequences of DNA associated with genetic alterations in tumors of the head and neck. In particular, the studies on relations between instability of micro-satellite sequences and expression of MLH1, MSH2, PMS1, PMS2 genes have been reviewed. Further aim of this study is to present preliminary results of a research project into distribution of hMLH1 and hMLH2 proteins in oral tissues. METHODS: Nine formalin fixed and paraffin embedded samples (8M/1F; mean age 58 years) of oral squamous cell carcinomas tissues have been analysed for the presence of hMSH2 and hMLH1 by using streptavidin-biotin immunoperoxidase technique. Samples have been analysed by optical microscope by two observers evaluating the positive cell percentage for three representative fields. RESULTS: Immunohistochemistry demonstrated that hMLH1 and hMSH2 are widely expressed nuclear proteins in oral tissues. CONCLUSIONS: The localization of hMLH1 and hMSH2 in oral epithelium are consistent with the biochemical function of these proteins in DNA mismatch repair.
Abstract: Between 1986 and 1996, 263 patients, 156 females and 107 males, affected by oral lichen planus (OLP), were followed at the Division of Oral Medicine and Pathology, University of Naples 'Federico II', Italy, and at the Institute of Dentistry and Maxillofacial Surgery, University of Bari, Italy. During this follow-up, the possible association of OLP with oral squamous cell carcinoma (SCC), together with the possible association of OLP, oral SCC and chronic HCV-hepatitis, were investigated. 14 cases (5.32%) were known to have developed oral SCC: 10 (3.8%) in an area of pre-existing OLP, 3 (1.14%) in other sites, in 1 case the diagnosis of OLP and SCC was synchronous (0.38%). 3 patients were positive for anti-HCV antibody. Many carcinomas were in areas of reticular/plaque OLP. 3 patients had multiple simultaneous sites of oral involvement (21.42%); 5 patients developed oral SCC in different sites during the follow-up period (35.71%). These data, together with a clear histological evidence of progression to carcinoma within OLP lesions, suggest the probability of some cases of at least OLP having an intrinsic property predisposing to neoplastic transformation, confirming previous studies. For these reasons, the authors think that it is necessary to follow-up the patients regularly at least annually and possibly for life for the early diagnosis of a possible neoplastic degeneration. These consideration are particularly important in the case of atrophic or erosive OLP, and plaque OLP, especially when involving the dorsum of tongue.
Abstract: A case of fibrosarcoma in a 4-year-old male child is reported. Primary fibrosarcomas of bone in the head and neck region are rare. The histological appearance of the tumour is related to its grade of differentiation. It could present a high level of cellularity and the amount of collagen is variable. The accepted treatment is radical surgery; however, metastases could occur in the lungs. This article is presented to highlight the rarity of fibrosarcomas in the jaws of children.
Abstract: The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.
Abstract: BACKGROUND: The authors examined 15 cases of in situ and early oral SCC to detect the presence of HPV genoma. METHODS: They proceeded to in situ hybridization on paraffined specimens utilizing DNA-biotinylated fragments in commercial kit (Vyra Type in situ, Life Technologies, Gaithersburg, MD, USA). RESULTS: HPV-DNA was detected in 9 cases: 6/11, 16/18, 31/33/35 serotypes were detected. The distribution of viral serotypes by sites showed a prevalence of 16/18 serotype in tongue and floor of the mouth carcinoma, a prevalence of 6/11 serotype in gingiva, hard palate and buccal mucosa carcinoma, and 31/33/35 in commissura. CONCLUSIONS: The results suggest an important role of HPV in oral carcinogenesis, but further investigations are necessary to confirm these data on larger groups of patients to obtain a higher significance of the results.
Abstract: Eighteen patients, ten affected by pemphigus vulgaris and four affected by herpes simplex of the oral mucosa, together with four healthy patients as controls, were investigated by cytologic examination of Papanicolaou stained smears obtained by scraping the oral mucosa. In all cases additional smears were immunostained with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies against human heavy IgG chains and lambda light chains. The results have shown that, for a cytological diagnosis of pemphigus, this technique can be used as an easy substitute for the immunofluorescence test and does not require any specialized training or equipment. The findings are clearly detectable by light microscopy and allow, together with the immunostaining, an adequate visualization of cell morphology.
Abstract: A morphometric study of silver-stained nucleolar organiser regions (NOR) was performed on histological sections from routinely paraffin-embedded blocks of 26 oral biopsy specimens (21 cases of leukoplakia consisting of 13 low, 4 moderate, 4 severe degree of dysplasia, and 5 cases of microinvasive carcinomas). In situ hybridisation (ISH) for HPV-DNA was performed on serial sections of the same samples. The following parameters were studied: V NOR (single AgNOR volume per nucleus), TV NOR (total AgNOR volume per nucleus), and R.I. (AgNOR's roundness index). The results highlight that not all the morphometric features of AgNORs allow the discrimination between lesions with dysplasia of low, moderate and severe degree and microinvasive carcinoma. TV NOR appeared useful, while the other morphometric parameters appeared statistically not significant i differentiating between the different lesions. These findings suggest that high values of TV NOR in oral dysplasia could represent a risk marker, identifying a subgroup of lesions with a worse prognosis, constituting then a possible indication for rigorous clinical management and/or for complex treatment of these HPV-associated preneoplastic lesions.
Abstract: The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.
Abstract: A case of granular cell ameloblastoma (GCA) was studied by light microscopy and histochemistry. Microscopically, the lesion showed small groups or large clusters of granular neoplastic cells, with pyknotic and hyperchromatic nuclei, oriented away from the basement membrane, in a back-to-back arrangement. The "granular change" is thought to be due to a dysfunctional status of neoplastic cells, and the pathogenesis of this tumour seems to be age-related. The prognosis of GCA is good, generally corresponding to that of the classical ameloblastoma; as yet, only one case has been described with a more aggressive biological behaviour (high recurrence rate).
Abstract: The authors reported a case of desmoplastic variant of ameloblastoma. The patient showed a swelling in right emi-mandible in the premolar region with radiologic features of fibro-osseous lesion (mixed radiolucent-radiopaque appearance). The histological diagnosis has been the only identifications instrument.
Abstract: Ten cases of odontogenic myxoma were evaluated radiologically, histologically, and histochemically. Ultrastructural examination was performed in five cases. Stellate cells with branching processes were seen in an abundant acid mucopolysaccharide background. Occasionally macrophages were found in the tumors. In two cases islands of inactive odontogenic epithelium were identified. The ultrastructural features suggest that many lesional cells are very similar to a myofibroblast. With the avidin-biotin complex immunohistochemical technique, the lesions were tested with antibodies to S- 100 protein, neuron-specific enolase, neurofilaments, glial fibrillary acid protein, keratin, desmin, muscle-specific actin, and vimentin. All the lesions were found to be positive for vimentin and muscle-specific actin, and negative for the rest. The results of our study seem to confirm the muscle-specific actin-positivity of odontogenic myxomas as previously reported.
Abstract: A typical case of Cowden disease is presented. This is rare mucocutaneous disease, genetically determined, with multiple organ system involvement in which a malignancy, particularly of breast and thyroid gland, may develop. The disease can be diagnosed in its early stages by gingival and cutaneous manifestations. We emphasize that the dentist may be the first health care professional who recognizes the syndrome, which is a crucial step to prevent and cure the predictable malignancy.
Abstract: A case of traumatic carotid-cavernous sinus fistula (CCSF) is presented. The patient sustained an undisplaced fracture of his right mandibular condyle and a zygoma fracture after a motor vehicle accident. Five months later, all the classic signs and symptoms of a CCSF had appeared except ophthalmoplegia. These symptoms were preceded by a tiring auditive homolateral sensation. A carotid angiography confirmed the presence of a large CCSF. Successful management was achieved intravascularly by balloon embolization.
Abstract: Nucleolar Organiser Regions (NORs) and Proliferating Cell Nuclear Antigen (PCNA) were investigated on routine paraffin embedded histologic sections of 30 oral biopsy specimens (six cases of leukoplakia with low-degree of dysplasia, nine cases of leukoplakia with moderate-degree of dysplasia, nine cases of leukoplakia with severe-degree of dysplasia, six cases of squamous microinvasive carcinomas), tested for HPV-DNA by in situ hybridisation (ISH). The absolute number of NORs per nucleus and the percentage of nuclear positivity for PCNA were found to be different in each group of pathology, with further diversity due to the presence or absence of HPV-DNA. In the major part of HPV-positive lesions, the AgNOR number and percentage of cells positive for PCNA were found to be generally lower than in corresponding negative forms. Conversely, a few cases of HPV+ lesions showed significantly higher values both of AgNOR and PCNA, if compared to the other cases of HPV+ and HPV- lesions. These data suggested that high values of AgNOR and PCNA, in moderate and high grade oral dysplasia, could represent an "alarm signal" of a worse prognosis, and then a possible indication for a strict clinical management and/or a stronger treatment of some HPV-associated preneoplastic lesions.
Abstract: Myxoma of the jaw is a rare odontogenic tumor, probably derived from the dental apparatus. The case described here was studied by both light and electron microscopic methods. Stellate cells with branching processes were reported in an abundant acid mucopolysaccharide stroma, and ultrastructurally these cells were seen to be fibroblast. Occasionally myxoblasts and macrophages were reported in the tumor. No odontogenic epithelium was identified, while an intracellular synthesis of cross-striated fibrils was observed. The ultrastructural features suggest that the connective tissue cell is the proliferating component of the tumor and is very similar to a fibroblast.
Abstract: A case of peripheral ameloblastoma, a rare odontogenic tumour, is presented. This tumour appears to differ from endo-osseous ameloblastoma by the absence of local malignancy. It exhibits a less aggressive and destructive behavior and does not invade the underlying bone. Conservative treatment of the tumour is the treatment of choice.
Abstract: A gingival localization of fibrosarcoma of soft oral tissues was described in a 58-year-old female. Primary fibrosarcoma of the head and neck region is rare. The histological appearance of the tumour is related to its grade of differentiation. The amount of collagen is variable. The accepted treatment is radical surgery; but metastases occur frequently in the lungs.
Abstract: The paper reports the findings of a study of 46 subjects affected by beta-thalassemia major who underwent periodic transfusion therapy. A reduced incidence of the caries process was observed, above all in subjects treated from the first months of life. After a short review of the main problems posed by these patients during dental treatment, the Authors propose a course of preventive antibiotic treatment to be carried out before the start of dental work.
Abstract: The paper reviews the literature on oral modifications presented by subjects affected by beta-thalassemia, an hereditary hemopathy present in significant numbers in some areas of Italy. Following a description of the clinical characteristics of the disease, the paper focuses on the genetic alterations leading to the hemopathy and their implication in the onset of the thalassemic state.
Abstract: The Authors, after a short description of the anatomy of the root canal, deal with the aetiological factors of the periapical pathology, acute and chronic. They examine the pathogenetic mechanisms of acute flogistic process of the periapical tissue and consider the principal mediators involved in the tissue lesion.
Abstract: A double-blind versus placebo clinical study has been carried out in order to assess the antiinflammatory and analgesic activity of nimesulide suppositories in pain-inflammatory pathologies of odontostomatological nature. Forty-four patients aged between 18 and 62 were recruited for the purpose and assigned at random to treatment with nimesulide or placebo for a minimum period of 3 days. Treatment with nimesulide reduced both the pain and the tumefaction due to the inflammatory pathology more rapidly and, by the 3rd day of treatment led to complete remission of the symptomatology. Tolerability of nimesulide was excellent.
Abstract: The Authors describe the aetiological mechanisms of periapical diseases. They deal with immunologic reactions in inflammation with particular features on the lymphocytic and macrophagic products and their role in the periapical reactions. Furthermore, they describe the pathogenesis of bone resorption, a common evolution of the chronic periapical disease.
Abstract: A clinical case of focal dermal hypoplasia or Goltz syndrome is described with details of the odontostomatological features both generally encountered and observed in the present case. The main aetiopathogenic hypotheses are also discussed and a dominant X-linked transmission is postulated.
Abstract: A case of ameloblastoma located at the upper maxillary, a site that is rare according to the literature, is reported. A perfect cure was obtained with conservative treatment without recurrence, as is shown by the four-year follow-up.
Abstract: The literature on the subject is reviewed, special attention being paid to the complex problems of aetiological and pathogenetic classification involved by such lesions in the oral cavity. Stress in salso laid on topographical and histological aspects of pigmented lesions of melanocytic origin.
Abstract: The aetiopathogenetic and evolutive problem of primary oral melanoma is examined with particular regard for melanosis and its relationship with oral naevi. These lesions are classified differently by Authors with different opinions regarding their ability to turn malignant. In this regard, the latest and most reliable hypotheses on the subject are put forward.
Abstract: A rare case of a primary malignant melanoma of the upper alveolus with rapid spread to the cervical lymph nodes and brain in a 47-year-old man is described.
Abstract: After reporting some statistics, the procedures used in the dental treatment of the heart surgery patients subjected to anticlotting pharmacological treatment are described. Considering the considerable difficult in implementing the necessary pharmacological modifications and the high percentage of possible complications involved in these procedures, maximum interdisciplinary cooperation is recommended with heart surgery colleagues so as to carry out dental treatment in good time in patients who are candidates for heart and large vessel operations.
Abstract: The biological causes of edentulous alveolar crest reabsorption are examined in the light of recent discoveries on the physiopathology of bone metabolism. The main techniques used for the classification of patients in terms of bone metabolism type are then described and the question of whether any currently available pharmacological treatment is capable of preparing for, supporting, preserving or even effectively replacing preprosthetic surgery is posed.
Abstract: The Authors describe the Burning Mouth Syndrome or B. M. S., a disorder that is characterized by stomatopyrosis, glossodynia " sine causa" with a specific psychological and ormonal condition. Furthermore they deal with the aetiopathogenetical hypothesis and the diagnostic and therapeutic protocol of B. M. S.
Abstract: Following a short review of the main aetiopathogenetic theories on dental agenesia, a personal statistical study of this pathology is reported. 1529 orthopantomographs of juveniles aged between 7 and 14 were examined. 79 cases of hypodentia were observed (5.2%), 32 in males (4.05%) and 47 in females (6.78%). The most interesting tooth was the second premolar with an incidence of 58.9% followed by the lateral incisor, with an incidence of 26.38%. This is in agreement with the international literature.
Abstract: The authors explained, after an attentive review of literature, the clinic and therapeutic procedures about dental germs' transplant. They show the indications for this surgical operation, the procedure for selection of grafting germs and the current surgical technique to do it.
