Synchronous endometrial and ovarian cancer: A case report.

BACKGROUND: Synchronous endometrial and ovarian cancer (SEOC) is a rare genital tract tumor. Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer (EC) or OC. In this review we present 2 cases of women who were diagnosed with SEOC, and discuss the clinical characteristic of SEOC, diagnostic and molecular profiling issues. Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples. CASE SUMMARY: In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC. They underwent surgical treatment and staging. Next-generation sequencing of 10 gene-panel identified CTNNB1, PIK3CA, and PTEN gene mutations in ovarian tissue in one case, while none of these genes were mutated in other case. Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage. CONCLUSION: Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.

ARID1A, NOTCH and WNT Signature in Gynaecological Tumours.

Ovarian cancer (OC) is among the deadliest gynaecologic malignancies in the world. The majority of OC patients are diagnosed at an advanced stage, with high-grade serous OC (HGSOC). The lack of specific symptoms and suitable screening strategies lead to short progression-free survival times in HGSOC patients. The chromatin-remodelling, WNT and NOTCH pathways are some of the most dysregulated in OC; thus their gene mutations and expression profile could serve as diagnostic or prognostic OC biomarkers. Our pilot study investigated mRNA expression of the SWI/SNF chromatin-remodelling complex gene ARID1A, NOTCH receptors, WNT pathway genes CTNNB1 and FBXW7 mRNA expression in two OC cell cultures as well as 51 gynaecologic tumour tissues. A four-gene panel consisting of ARID1A, CTNNB1, FBXW7 and PPP2R1A was used to investigate mutations in gynaecologic tumour tissue. All seven analysed genes were found to be significantly downregulated in OC when compared with non-malignant gynaecologic tumour tissues. NOTCH3 was also downregulated in SKOV3 cells when compared to A2780. Fifteen mutations were found in 25.5% (13/51) of the tissue samples. ARID1A predicted mutations were the most prevalent with alterations detected in 19% (6/32) HGSOC and 67% (6/9) of other OC cases. Thus, ARID1A and NOTCH/WNT-pathway-related changes could be useful diagnostic biomarkers in OC.

Uterine Cavity Lavage Mutation Analysis in Lithuanian Ovarian Cancer Patients.

BACKGROUND: Type II ovarian cancer (OC) is generally diagnosed at an advanced stage, translating into a poor survival rate. Current screening methods for OC have failed to demonstrate a reduction in mortality. The uterine lavage technique has been used to detect tumor-specific TP53 mutations from cells presumably shed from high-grade serous ovarian cancer (HGSOC). We aimed to pilot whether the detection of TP53 mutation in uterine cavity lavage can be used as a diagnostic method for HGSOC using an expanded gene panel. METHODS: In this study 90, uterine lavage and 46 paired biopsy samples were analyzed using next-generation sequencing (NGS) targeting TP53 as well as five additional OC-related genes: BRCA1, BRCA2, PI3KCA, PTEN, and KRAS. RESULTS: Uterine lavage was successfully applied to all patients, and 56 mutations were detected overall. TP53 mutations were detected in 27% (10/37) of cases of type HGSOC; BRCA1 and BRCA2 mutations were also frequent in this group (46%; 17/37). Overall concordance between tissue and liquid biopsy samples was 65.2%. CONCLUSION: Uterine lavage TP53 mutations in combination with other biomarkers could be a useful tool for the detection of lowly invasive HGSOC.

Future Screening Prospects for Ovarian Cancer.

Current diagnostic tools used in clinical practice such as transvaginal ultrasound, CA 125, and HE4 are not sensitive and specific enough to diagnose OC in the early stages. A lack of early symptoms and an effective asymptomatic population screening strategy leads to a poor prognosis in OC. New diagnostic and screening methods are urgently needed for early OC diagnosis. Liquid biopsies have been considered as a new noninvasive and promising method, using plasma/serum, uterine lavage, and urine samples for early cancer detection. We analyzed recent studies on molecular biomarkers with specific emphasis on liquid biopsy methods and diagnostic efficacy for OC through the detection of circulating tumor cells, circulating cell-free DNA, small noncoding RNAs, and tumor-educated platelets.

Endometrial biopsy and density of nerve fibers in eutopic endometrium. Looking for easier ways to diagnose endometriosis.

The purpose of study was to evaluate if there is any difference between nerve fibers density in eutopic endometrium in women with and without endometriosis. The prospective case - control study conducted between October 2013 and December 2015. The study included 60 reproductive age women undergoing laparoscopy for suspected endometriosis, pelvic pain, or infertility and not currently receiving hormonal treatment for at least 3 months prior to laparoscopy. Immunohistochemical nerve fiber detection in endometrial curetting using anti-gene product 9.5 was compared with surgical diagnosis. The nerve fibers were detected in eutopic endometrium in women with and without endometriosis. PGP9.5 positive nerve fibers were found in 26 (43%) cases: 16 (50%) in women with endometriosis and 10 (36%) in women without endometriosis. The mean nerve fiber density was higher in the group with endometriosis (0.53 per mm2 ± 0.68) than without endometriosis (0.48 per mm2 ± 0.89), but no statistically significant difference was observed (p > .05). Test specificity was 64.3%, sensitivity 50%, positive predictive value - 61.5%, negative predictive value - 52.9%, and overall accuracy 56.7%. The detection of PGP9.5 positive nerve fibers in eutopic endometrium cannot be used as a reliable diagnostic test of diagnosing endometriosis.