Abstract: Studies on the association between the Ile to Val polymorphism at codon 655 of the human epithelial growth factor receptor 2 (HER-2) gene and susceptibility to breast cancer have been reported for almost all ethnic populations, with both positive or negative conclusions. No study, however, has yet been focused on the possible association between this gene and its predisposition to benign breast lesions, especially on risk for fibroadenoma. We aimed to study the association of the single nucleotide polymorphism V655 HER-2 gene polymorphism with histologically verified breast fibroadenoma risk. We conducted a molecular epidemiological case-control study of 70 breast fibroadenoma cases without cellular atypia and 172 healthy female controls. We found that the Val variant allele and genotype frequency of this polymorphism is higher in cases with fibroadenoma; however, this difference was not significant (allele Val 655: 27.86 and 22.67% in fibroadenoma and controls, respectively; genotype Ile/Val: 35.71 and 38.37% and Val/Val: 10.0 and 3.49% in fibroadenoma and controls, respectively). Applying logistic regression analysis, we found an increased risk of fibroadenoma formation in carriers of the Val allele (odds ratio=1.17; 95% confidence interval=0.67-2.05), in which the highest risk was associated with homozygous genotype (odds ratio=3.07; 95% confidence interval=0.97-9.72), but this risk was not significant. Stratification by age (cut-off 45 years) revealed the highest risk of fibroadenoma among young women homozygous for the Val allele (odds ratio=3.30). The risk, however, was slightly increased (odds ratio=1.24) among older carriers of the aberrant allele in their genotype as well, but it was not significant. In spite of insignificant differences, our results indicate that HER-2 Ile655Val polymorphism, especially in a homozygous form might play some role in the etiology of breast fibroadenoma formation. The significance of this susceptibility, however, will have to be verified by larger studies.
Abstract: Spontaneous regression of malignant tumors is a rare event. It is defined as partial or total disappearance of a proven malignant tumor without adequate medical treatment. The causes of this phenomenon are various. Nevertheless, malignant tumors do regress occasionally for no apparent reason, as evidenced by many clinical observations. We report a case of a 68-year-old woman, who was presented with a several-month history of a painless firm lump, initially of 1 cm in diameter and growing to a large solid regular tumor of 2.5 x 2.5 cm in size, in the upper outer quadrant of her right breast. Preoperative histopathological diagnosis revealed ductal invasive carcinoma. Later on, while awaiting surgical treatment, she suffered an arm injury requiring a 1-month delay of surgery. After recovery, on the date of surgery the tumor disappeared, and, in addition, it was not found in tissue specimens obtained from quadrantectomy. After 78 months of follow-up there was no evidence of relapse. In this report, we discuss clinical and histopathological findings, patient management and possible mechanisms of cancer regression.
Abstract: Objectives: To assess ductus venosus (DV) indices during the first stage of labor and the effect of ruptured membranes, meconium stained liquor and epidural analgesia (EDA). Methods: Prospective cross-sectional study. Eighty-one women with low-risk singleton term pregnancies participated, 51 had normal labor (Group 1), and 30 experienced ruptured membranes and/or stained liquor (Group 2). Of the latter group 14 received EDA. The effect of various interventions and application of EDA on the ductus venosus index (DVI) and pulsatility index for veins (DV PIV) were tested. Results: The feasibility rate was 94%. A significant increase of DV indices (DVI, DV PIV) was found in group 2 (P<0.001 and P<0.0005, respectively). The A-velocity was also significantly lower in group 2 (P<0.02). A markedly significant increase of DV indices (P<0.0001) among participants receiving EDA was observed in group 2. The mean+/-SD indices were: 0.53+/-0.10 for the DVI and 0.68+/-0.14 for the DV PIV in those women. There was a significant positive correlation of DV indices with the duration of amniorrhea in group 2 (PIV: r=0.66; P<0.002; DVI: r=0.68; P<0.001). Conclusions: Long-term amniorrhea seems to affect the fetal venous circulation reflected in increased DV waveform indices.
Abstract: The human multidrug resistance gene 1 (MDR-1) encodes a plasma membrane P-glycoprotein (P-gp) that functions as the transmembrane efflux pump for various structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR-1 gene may have an impact on the expression and function of P-gp, thereby influencing the susceptibility to various diseases, including cancer. We investigated the incidence of C3435T polymorphisms at exon 26 in the MDR-1 gene in 92 women with breast cancer and potential association of altered genotypes with smoking and high body mass index in cancer development among patients. The MDR-1C3435T allelotype and genotype analysis revealed a high incidence (75.0%) of polymorph alteration in the MDR-1 gene. The frequencies of homozygous T/T, heterozygous C/T and homozygous C/C genotypes were 25.0, 50.0 and 25.0%, respectively. The risk of breast carcinoma in patients with MDR-1 polymorphism was significantly associated with the higher body mass index, where women with BMI >30 kg/m(2) and C allele in genotype had a higher risk of disease compared to patients with lower amounts of body fat tissue (p=0.0439). The risk was highest for the homozygous carriers of C allele with BMI >30 kg/m(2) compared to patients with BMI 25.1-30 or <or=25 kg/m(2) (OR 3.65, 95% CI 0.94-14.20; or OR 2.50, 95% CI 0.55-11.41), respectively. Consistent with the results of genotyping and BMI analyses, smoking patients harboring the C/T or C/C genotype had an increased risk of cancer (OR 1.28, 95% CI 0.23-7.17; OR 1.58, 95% CI 0.28-10.44, respectively) when exposed to carcinogens in tobacco smoke, although it was not statistically significant. Our findings suggest that the MDR-1C3435T polymorphism occurs in high incidence among women with breast carcinoma where C allele carriers have increased risk of developing cancer when exposed to toxic substances. Our observations are the first that indicate this polymorphism as a modulator of health to be associated with an increased risk of breast cancer.
Abstract: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that occurs preferentially in the pleura. Although it has been described at some extrathoracic sites, its occurrence in the female genital tract is extremely rare. We are the first to report on an unusual case of a large (14cm in the largest diameter) SFT localized in the broad ligament of the uterus in a 50-year-old woman. The patient underwent surgical tumor extirpation and has remained well without any sign of local tumor recurrence after 6 years of follow-up. We discuss the clinical aspects, the gross macroscopic appearance, the histologic findings, and the differential diagnosis, and provide a review of the literature.
Abstract: Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. As a transcription factor p53 controls many cell processes and helps in prevention of cancer development. The p53 gene is polymorphic. Polymorphisms can affect the important regions involved in protein tumor suppressor activity. The well-known polymorphisms are the polymorphisms BstUI in exon 4 and MspI in intron 6. Both are supposed to be associated with cancer development. The purpose of this study was to investigate the genotype frequencies and associations of these polymorphisms with breast cancer in Slovak population. We observed the prevalence of BstUIPro (27.47%) and MspIA1 (17.58%) alleles and BstUIPro/Pro (8.79%) and MspIA1/A1 (5.49%) genotypes in breast cancer patients in comparison with controls 23.40%, 14.10%, 5.77%, 1.92% respectively. However the differences were not significant. After division of the cases and controls according to the age the prevalence of the risk alleles and genotypes in women at the age 50 years or less was higher as compared to women older than 50 years. In the younger women group, the p53 BstUI polymorphism genotype frequencies were 6.2% for BstUIPro/Pro, 31.0% for BstUIArg/Pro and 62.8% for BstUIArg/Arg in controls and 11.11 %, 40.74% and 48.15% in cases respectively. The risk of disease for BstUIPro/Pro genotype was more than two-fold higher in comparison with the BstUIArg/Arg (OR=2.34, 95% CI=0.53-10.24). In p53 MspI the genotype frequencies were 1.77% for MspIA1/A1, 24.78% for MspIA1/A2 and 73.45% for MspIA2/A2 in controls and 11.11%, 18.52% and 70.37% in cases respectively. The risk of disease for MspIA1/A1 genotype was more than six-fold higher in comparison with the MspIA2/A2 (OR=6.55, 95% CI=1.02-41.98). When we evaluated the association of both polymorphisms together with the breast cancer risk we observed that the highest risk was connected with the genotype BstUIPro/Pro / MspIA1/A1 (OR=2.99, 95% CI=0.69-13.06). Our results indicate that both BstUI and MspI p53 polymormphisms might play the role in the breast cancer development especially in women younger than 50 years.
Abstract: Carcinosarcomas (CSs) are rare biphasic neoplasms of the female genital tract, with the presence of malignant epithelial and mesenchymal components. The occurrence of non-epithelial or non-mesenchymal differentiations in CSs is extremely rare. A case of a 54-year-old woman with a history of treatment for breast carcinoma is reported. The patient presented with a uterine tumor showing histological, immunohistochemical, and ultrastructural features of an extremely rare CS, with signs of melanocytic differentiation. The lesion was a 7.0x5.6cm polypoid tumor mass arising from the endometrium and metastasizing in the abdominal cavity as a malignant melanoma - the most aggressive component of CS. Despite adjuvant chemotherapy, she died 8 months after the initial diagnosis due to the metastatic spread of CS. In line with current knowledge, we assess the melanocytic differentiation as one of a hypothetic differential line with the ability of multidirectional stem cell differentiation. We discuss a possible pathogenesis of this lesion and the role of tamoxifen in the tumor development as well. To the best of our knowledge, only one case of uterine CS with melanocytic differentiation has been reported in the English literature.
Abstract: Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development. The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP method. The DNA was isolated from white blood cell nuclei. The frequency of Val allele in the cancer group was 29.79% and was higher than in the control group 15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 46.81% of patients in the case group and in 28.33% in healthy individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67, respectively (p<0.01). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR=2.90), among women with positive family history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5). Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val allele carriers (OR=0.3). In conclusion, this study revealed relatively high frequency of the Val allele among the women population of the Slovak republic. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.
Abstract: OBJECTIVE: To analyze the effects of uterine contractions on ductus venosus (DV) pulsatility during the first stage of labor. METHODS: Twenty healthy women were examined. Measurements were taken at three stages of cervical dilatation (<4 cm, 4-7 cm and >or=8 cm) during and between contractions. Peak velocity during ventricular systole (S) and atrial contraction (A), pulsatility index for veins (DV PIV), ductus venosus index (DVI) and the S/A ratio were measured. RESULTS: The DV was observed successfully in 16 cases. The mean S velocity did not change significantly (64 cm/s during and 65 cm/s between contractions). The mean A velocity decreased significantly from 35 cm/s measured between contractions to 29 cm/s during contractions (P<0.0001). The mean DV PIV and DVI were significantly higher during contractions (0.72 and 0.55) than between contractions (0.57 and 0.45) (P<0.0001). There were no significant differences in means between stages of cervical dilatation. CONCLUSION: Significant differences during and between uterine contractions can be observed in DV pulsatility during normal labor.
Abstract: It is known that BRCA genes play central roles in hereditary breast and ovarian cancers. BRCA1 mutation carriers face a cumulative lifetime risk of ovarian and breast cancer development. We report on a case of a strong family prevalence of BRCA1 linked malignancies as an immense psychological encumbrance and reason of demand for radical prophylactic risk decreasing surgeries in a 29 year-old healthy woman with proved 3889delAG BRCA1 gene mutation on exon 11, codon 1265 in effort to prevent possible malignant changes in the ovaries and the breast. Problems regarding the management of asymptomatic BRCA mutation carriers, time and impact of early prophylactic surgery in young women are discussed with a review of recent literature.
Abstract: OBJECTIVE: To assess feasibility and physiological variation of fetal ductus venosus Doppler velocimetry during the first stage of labor between uterine contractions. STUDY DESIGN: A prospective cross-sectional study including 23 healthy women with low-risk pregnancies. Maximum velocities during ventricular systole (S) and atrial contraction (A) were recorded in the ductus venosus between contractions. Pulsatility index for veins (DV PIV) and the ductus venosus index (DVI) were also calculated. SETTING: Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University, Martin. RESULTS: Acceptable ductus venosus waveforms were acquired in 19 fetuses (83%). The mean +/- SD values of the ductus venosus index and the pulsatility index were 0.46 +/- 0.07 (95% CI: 0.42-0.49) and 0.57 +/- 0.12 (95% CI: 0.51-0.63), respectively. The mean +/- SD values of maximum velocities during ventricular systole (S) and atrial contraction (A) were 65 +/- 8 cm/s and 35 +/- 5 cm/s, respectively. CONCLUSION: Ductus venosus blood flow velocities can be assessed during labor. This calls for an extension of the detection possibilities of intrauterine fetal status and gives an idea to establish reference ranges for these circulation parameters during labor in the future.
Abstract: Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare benign proliferation of mesenchymal stromal cells with irregular slit-like formations resembling angiomatous structures. In the majority of cases this lesion is a focal microscopic finding in breast biopsies performed for benign or malignant diseases. It may present in a pure diffuse or nodular form. The exact etiology and pathogenesis of this tumor-like lesion is still unknown, but a proliferative response of myofibroblasts to hormonal stimuli has been postulated. A large 12 x 9 x 3.5 cm rapidly growing nodular form of PASH of the breast in an 18-year-old woman is here described with clinical and histological findings. A possible hormonal etiology was indicated by elevated progesterone (three-fold) and decreased estrogen serum levels. Different diagnostic lesions, such as giant fibroadenoma and low-grade angiosarcoma, are discussed. To the authors' knowledge this is only the fourth case of nodular PASH of the breast reported in the English literature.
Abstract: OBJECTIVE: The aim of this study was to analyze the incidence, causes and management in women with chronic pelvic pain and to evaluate the role of laparoscopy. DESIGN: A prospective non-randomized clinical trial on 86 women with chronic pelvic pain. SETTING: Clinic of Gynecology and Obstetrics, JMF CU Martin, Slovak Republic. METHODS: A prospective clinical trial was performed on 86 patients with chronic pelvic pain, who have undergone laparoscopy from March 2003 to March 2004. Only patients with a pain history of at least 6 month were enrolled into this trial. Specific patient's history characteristics, laparoscopic and cytologic findings were reviewed and analyzed (pain interval, organic findings, preoperative ultrasound examination, previous surgical intervention, oral contraceptive usage, patient's medical history, menstrual cycle regularity, age, presence of dysmenorrhea). In all women, laparoscopy was performed under general anesthesia. RESULTS: During the study we have performed 309 diagnostic laparoscopic examinations, from which 86 (27.8%) were done due to chronic pelvic pain. The mean patient's age was 35.8 years (19-56). The mean parity was 1.6, ranging from 0-5. Pelvic organ pathology was present in 88.4% of the patients. The most frequent finding was endometriosis (31.4%). According to revised criteria of the American Fertility Society the presence of first, second, third and fourth stage of endometriosis was 55.6, 25.9, 11.1 and 7.4%, respectively. The most frequent occurrence of endometriotic lesions were on ligamenta sacrouterina (21.4%) and plica vesicouterina (19.0%). Pelvic adhesions, myomas, pelvic varicosities and chronic inflammatory process were present in 25.6, 15.1, 9.3 and 3.5% of the cases, respectively. No somatic origin of pain was identified at laparoscopy in 11.6% of patients. Preoperative ultrasonic examination with pelvic pathology findings were performed in 36 patients, and laparoscopy correlated with ultrasonographic findings in 31 (86.1%) cases. The average pain duration was 11.5 months (6-28) with the majority among women with history of previous surgical intervention (48.8%) and parturated women. Presence of pain was most common among women after 31 years of age. Predominantly, cytology examination of biological materials (peritoneal fluid, cyst fluid) revealed an increased histiocytic reaction in coincidence with chronic inflammation process in 31.6%. CONCLUSION: Invasive laparoscopy in chronic pelvic pain pertains to one of the most important examination procedures for its high specificity and sensitivity. Laparoscopy can reveal organic causes of pelvic pathology in 60% of cases with the possibility of following treatment. Our combined effort should stop the progression of such pathology leading to possible morphologic, functional and psychological alteration, especially among young women in fertile age. Today, endometriosis still remains the main cause of chronic pelvic pain in high percentage rate.
Abstract: We report on a 50-year-old female patient affected by breast cancer and a tumorous lesion located in the subserosal and intramural part of the uterine fundus. It consisted of glandular and cystic forms lined with epithelium of the tubal type. We describe the clinical, macroscopic, and histological features of this rare non-neoplastic lesion, classified as florid endosalpingiosis (ES) and belonging to the spectrum of Müllerian lesions. The discussion focuses on its morphological characteristics, the differential diagnosis, and the potential reasons leading to its origin. To the best of our knowledge, this is the fifth case of florid ES of uterus reported in the English literature.
Abstract: OBJECTIVE: To determine serum levels of TNF-alpha (tumor necrosis factor alpha) as a prediction of endometriosis. DESIGN: Prospective clinical case control study. SETTING: Department of Obstetrics and Gynaecology and Department of Pathology, Jessenius Faculty Hospital, Kollarova 2, Martin, Slovakia. METHODS: The serum TNF-alpha was determined in women who underwent laparoscopy or laparotomy due to pelvic pain, infertility, dysmenorea or pelvic tumor. Endometriosis was confirmed histologically and classified by rAFS. RESULTS: On the basis of entering criteria 65 women were enrolled in this study. In 61 cases serum level of TNF-alpha was evaluated. The average serum level of TNF-alpha in the endometriotic group was 73.847 pg/ml (n=30) and without endometriosis was 21.089 pg/ml (n=31). We have found a significant statistical difference between the above mentioned groups in the medium levels of TNF-alpha (p<0.0001). We did not find statistical significance between TNF-alpha levels and in the group of women with endometriosis in relation to the stage of the disease (I.-II., III.-IV., adenomyosis). At a cut-off level of TNF-alpha 30 pg/ml there was a 63.33% sensitivity, 77.42% specificity, a positive prediction value 73.07%, and 68.57% of negative predictive value. CONCLUSION: TNF-alpha serum levels are good diagnostic markers of endometriosis in the spectrum of noninvasive methods.
Abstract: OBJECTIVE: To demonstrate a case of unrecognized endometrial cancer at endometrial ablation. SUBJECT: Case report. SETTING: Department of Obstetrics and Gynaecology and Department of Pathology, Jessenius Faculty Hospital, Martin, Slovakia. SUBJECT AND METHOD: Authors describe a case of an early endometrial cancer diagnosed from material obtained by bipolar loop electrode during endometrial ablation. CONCLUSION: Authors poing out insufficiency of curettage as a method of endometrial biopsy prior to ablation. Using of the loop electrode may minimize the incidence of unrecognized malignancies.
