ERß- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis.

In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-ß (ERß) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERß binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERß target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ERß at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ERß and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention.

Changes in the ovarian stromal blood flow in patients treated with laparoscopic salpingostomy for ectopic pregnancy.

This study is aimed to evaluate the impact of laparoscopic salpingostomy on ovarian stromal blood flow indices in patients with ectopic pregnancy, and to compare the ovarian stromal blood flow indices with matched paired healthy women. We included 37 patients who underwent laparoscopic salpingostomy and 37 age- and parity-matched women as controls. The main outcome was the differences in ovarian volume, antral follicle count (AFC), and ovarian stromal blood flow indices between the study group participants after the surgery and the healthy controls. Comparison of the ovarian parameters between the study group after the surgery and the control group revealed no significant differences in terms of ovarian volume (p = 0.783), AFC (p = 0.253), ovarian stromal S/D ratios (p = 0.054), pulsatility index (PI; p = 0.938) and resistance index (RI; p = 0.041). In addition, comparison of the ovarian parameters before and after the surgical treatment revealed no significant differences in the ovarian volume (p = 0.141), AFC (p = 0.084), ovarian stromal S/D ratios (p = 0.187), PI (p = 0.102) and RI (p = 0.108). In conclusion, laparoscopic salpingostomy does not affect ovarian function in terms of ovarian stromal blood flow indices, ovarian volume, and AFC.

Sexual dysfunction assessment and hormonal correlations in patients with polycystic ovary syndrome.

In this controlled study, we aimed to evaluate the sexual dysfunction of patients with polycystic ovary syndrome (PCOS) in comparison to healthy controls. We enrolled 64 sexually active women in our study. The PCOS group consisted of 32 women who met the Rotterdam diagnostic criteria, and the control group was composed of 32 age-matched, healthy females. In addition to the demographic and clinical characteristics of the participants, the hormonal and biochemical parameters were also studied. All patients were invited to fill out the female sexual function index (FSFI) and Beck's Depression Inventory questionnaires. The prevalence of sexual dysfunction in the PCOS group was similar to controls (25% vs 19%; P=0.54). No significant difference was found according to each domain score of FSFI. Significant negative correlations were found between the total FSFI scores of the PCOS group and the total (r=-0.278) and free testosterone (r=-0.493) levels. Although depressive scores of PCOS patients were higher, they did not show greater impaired sexual functions than age-matched controls according to their FSFI scores. Considering the multifactorial state of female sexual dysfunction, further studies are needed to clarify the impact of PCOS upon sexuality.

Comparison of risk of malignancy indices; RMI 1-4 in borderline ovarian tumor.

PURPOSE: The aim of this study was to evaluate prognostic values of the risk of malignancy index (RMI)/1-4 in patients with borderline ovarian tumors (BOTs). METHODS: The study consisted of 50 patients with BOT diagnosed and treated between 2005-2010 and 50 patients with benign adnexal massses between 2009-2010 as a control comparison group in the retropsective study. Preoperative serum CA125, U score, tumor size (S), and menopausal status were recorded. The RMI 1-3 was calculated according to the formula; UxMxCA125 and RMI4 formulation was; UxMxCA125xS. S equaled 1 for tumor size <7 cm and was 2 when size a 7 cm. The RMI 1-4 indices were calculated for all patients together with the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA). The performances of RMI indices were evaluated by McNemar's test and determined the best score cutoff value by the receiver operating characteristic (ROC) curve. RESULTS: The mean age, median value of CA125, ultrasound score, menopausal status, median values of RMI 1-4 of BOTs were statistically higher than benign adnexal masses. The sensitivity of RMI 1-4 was 26, 36, 62, and 60% at cutoff 200 level, respectively. The areas under curve of RMI 1-4 were found to be 0.676, 0.665, 0.668 and 0.734, respectively. DA of RMI 1-4 was found to be 56, 59, 50, and 71, respectively. When RMI 1-4 indices were compared with each other RMI 4 was the best RMI for BOTs. CONCLUSION: RMI 4 was the best predictive RMI for preoperative discrimination of BOT at a cutoff level of 200.

Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors.

OBJECTIVE: The aim of this study was to assess tumor markers and clinicopathological findings of patients with serous and mucinous borderline ovarian tumor (BOT) features. METHODS: The study consisted of 50 patients that were diagnosed with and treated for BOT between 2005-2010 in three centers. CA125, CA19-9, and CA125+CA19-9 levels and clinicopathological features were compared in serous and mucinous histotypes. In serous and mucinous BOTs, correlations between tumor markers and demographics such as age, menopausal status, parity, clinical findings (stage, relapse, adjuvant chemotherapy, cytology, lymph node involvement and tumoral morphology (cystic-solid content, papilla, septation) were evaluated. RESULTS: There were no significant differences between serous and mucinous tumors in the clinicopathological features such as stage, tumor markers, age, menopausal status, or cytology. In serous BOTs we found a significant relation between elevated CA125+ CA19-9, CA19-9 and recurrence (p < 0.05). Also there was a significant relation between elevated CA125+ CA19-9, CA19-9 and cytology positivity (p < 0.05). We found a significant relation in serous BOTs between elevated CA125+CA19-9, adjuvant chemotherapy and lymph node metastases (p < 0.05). Also In mucinous BOTs with papilla formation we found a significant relation between elevated CA125 and CA125+ CA19-9 (p < 0.05). There was significant relation between cytology positivity and elevated CA19-9 in mucinous BOTs (p < 0.05). CONCLUSION: Serum tumor markers of serous and mucinous BOTs were different in relation to their clinicopathological features. This may reflect differences of serous and mucinous BOTs.