Purpose: We aimed to determine the clinical role of the p53 family members p53 and p73 in the responsiveness to platinum-based chemotherapy and survival in ovarian cancer, considering their cross-talk and the p53 polymorphism at codon 72. Experimental Design: A detailed analysis of p53 and p73 in a series of122 ovarian cancers was done.We used a functional yeast-based assay to determine the p53 mutational status. Red yeast colonies, indicating mutant p53, were subsequently sequenced to determine the specific p53 alteration. p53 mutations were divided into two groups according to their previous characterization in the literature: those that efficiently inhibit transcriptionally activeTAp73 function and those that do not. A p53 polymorphism at codon 72 was determined in corresponding normal tissue or blood of ovarian cancer patients. Isoform-specific p73 expression analysis using real-time reverse transcription-PCR has previously been done in the majority of ovarian cancers included in this study. In a retrospective chart review, responsiveness to chemotherapy was assessed, and survival data with long follow-up times were collected. Results: Eighty of 122 (65.6%) of ovarian cancers harbored p53 mutations. p53 mutational status was an important determinant of responsiveness to platinum-based chemotherapy in all patients with a residual tumor of <2 cm in diameter after initial surgery (wild-type versus mutant, P = 0.029). In addition, p53 mutational status was a strong prognosticator for recurrence-free and overall survival (P < 0.0001and P = 0.003, respectively) in univariate analyses. High expression levels of dominant-negative p73 isoforms (DNp73 and DNVp73) significantly correlated with chemotherapeutic failure (P = 0.048) and with worse recurrence-free and overall survival in patients with p53 mutant cancers (P = 0.048 and P = 0.005, respectively). Eight p53 mutations, present in 19 cases, were found that efficiently inhibit TAp73 (i.e., 175H, 220C, 245S, 245D, 248W, 248Q, 266E, and 273H). Patients with p53 mutations that efficiently inhibit TAp73 function had a significantly shorter overall survival than patients with p53 mutations of unknown effect on TAp73 (P = 0.044). The p53 polymorphism at codon 72 had no influence on responsiveness to chemotherapy or survival. Conclusion: We provide the first clinical evidence that dominant-negative p73 isoforms contribute to drug resistance in vivo, underscoring the importance of a p53-p73 cross-talk. NH 2 -terminally truncated p73 isoforms were of significant clinical effect by providing an additional unfavorable factor for response to platinum-based chemotherapy and survival in p53 mutant ovarian cancers.

IntroductionWe analyzed the psychometric properties of the Polish version of the Hospital Anxiety and Depression Scale (HADS) in gynecologic patients.Material and methodsA total of 252 patients, consisting of three subgroups – endocrinologic gynecology (n = 67), high-risk pregnancy (n = 124), and outpatient gynecologic clinic (n = 61) – responded to the HADS, the 12-item Well-being Questionnaire (W-BQ12), the Spielberger State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory-II (BDI-II), and the Hamilton Depression Scale (HAMD). Socio-demographic data were obtained by self-report and interviews.ResultsThe HADS presented good internal consistency with Cronbach’s α at 0.84 and 0.78 for depression and anxiety subscales, respectively, and 0.88 for the whole questionnaire. The principal component analysis with Eigenvalues > 1 revealed a three-factor structure. Factors 1 (“depression”), and 2 (“anxiety”), as well as the separate Factor 3, explained 23.48%, 21.42%, and 12.07% of the variance, respectively. The items with shared loadings were A1, A3, and A6. The HADS scores correlated strongly with other depression and well-being scales, but not with STAI-X1/X2.ConclusionsThe Polish HADS revealed a three-factor structure, and 3/7 HADS-A items showed ambiguous factor loadings. All other psychometric properties were satisfactory. The HADS seems to be suitable for use in gynecologic patients, preferentially as an indicator for global psychological distress.

Myeloperoxidase (MPO) is an oxidant generating enzyme normally restricted to myeloid cells, however aberrant MPO expression has been found to occur in non-myeloid cells in some disease states. The functional -463GA promoter polymorphism alters MPO expression levels. The -463G is within an SP1 binding site and is associated with higher gene expression. The G allele is most frequent with ~62% of European populations being GG homozygotes. The GA polymorphism has been associated with risk or survival in a variety of cancers including lung and breast cancer. In this study we determined the frequency of the -463G/A polymorphism in 230 ovarian cancer patients, 75 patients with borderline ovarian tumors, and 299 healthy controls. The GG genotype was found to be overrepresented in patients with early stage ovarian cancer (83.3% GG, p = 0.008) as compared to healthy controls (62% GG), suggesting MPO oxidants may increase risk. Immunohistochemical analysis revealed MPO expression in a subset of columnar ovarian epithelial carcinoma cells in early stage carcinomas.

Platelets seem to play a role in the development of ovarian cancer. Platelet count (PLT) is an ubiquitous available parameter. We analyzed retrospectively data of 756 patients with primary adnexal tumors: 584 benign and 172 malignant (148 invasive and 24 borderline) cases. We compared the diagnostic accuracy of CA125, PLT, and a combination of CA125 and PLT. The cutoff values for CA125 and PLT were 35 U/ml and 350/nl, respectively. The median age of patients with benign and malignant tumors was 45 and 64 years, respectively. A total of 77/172 (44.8 %) malignant and 50/584 (8.6 %) benign cases presented with thrombocytosis (PLT ≥350/nl). The median PLT differed between benign and malignant cases (257/nl vs. 330/nl; p < 0.001), similarly as CA125 did (17 vs. 371 U/ml; p < 0.001). In the multivariate analysis, age, CA125, and thrombocytosis predicted independently the presence of malignancy. The results of CA125 were false positive in 21 % and false negative in 13 %. If considered together, thrombocytosis + CA125 were false positive only in 9 %, whereas the false negative rate was 12 %. The sensitivity and specificity of CA125, thrombocytosis, and thrombocytosis + CA125 for detecting adnexal malignancy were 0.88/0.78, 0.45/0.91, and 0.81/0.94, respectively. The positive predictive value (PPV) of CA125, thrombocytosis, and thrombocytosis + CA125 was 0.79, 0.61, and 0.91, respectively. In conclusion, PLT is an ubiquitously available parameter that could be useful in the diagnostic evaluation of pelvic mass. Considering thrombocytosis additionally to CA125 improves the specificity and PPV and reduces the false positive rate in detecting adnexal malignancy.

Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists’ experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma.

The mode of inheritance of hymenal variants has not been determined so far. Because surgical corrections of hymenal variants should be carried out in asymptomatic patients (before menarche), gynecologists and pediatricians should keep in mind that familial occurrences may occur.

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The human microbiome has been given increasing importance in recent years. The establishment of sequencing-based technology has made it possible to identify a large number of bacterial species that were previously beyond the scope of culture-based technologies. Just as microbiome diagnostics has emerged as a major point of focus in science, reproductive medicine has developed into a subject of avid interest, particularly with regard to causal research and treatment options for implantation failure. Thus, the vaginal microbiome is discussed as a factor influencing infertility and a promising target for treatment options. The present review provides an overview of current research concerning the impact of the vaginal microbiome on the outcome of reproductive measures. A non-Lactobacillus-dominated microbiome was shown to be associated with dysbiosis, possibly even bacterial vaginosis. This imbalance has a negative impact on implantation rates in assisted reproductive technologies and may also be responsible for habitual abortions. Screening of the microbiome in conjunction with antibiotic and/or probiotic treatment appears to be one way of improving pregnancy outcomes.