Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma.

Background there is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues. AIM: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients. PATIENTS AND METHODS: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60). RESULTS: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001). In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.

Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis.

OBJECTIVE: To compare the efficacy and safety of dienogest (DNG) with depot leuprolide acetate (LA) in patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. DESIGN: Prospective randomized trial. SETTING: Zagazig University hospitals, Egypt. PATIENTS: Two hundred and forty-two patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. INTERVENTION: Dienogest (2 mg/day, orally) or depot LA (3.75 mg/4 weeks, intramuscularly) for 12 weeks. MAIN OUTCOME MEASURES: A visual analogue scale was used to test the intensity of pain before and after the end of treatment. RESULTS: There was highly significant reduction in pelvic pain, back pain and dyspareunia in both groups with mean of difference in dienogest group (28.7 ± 5.3, 19.0 ± 4.3 and 20.0 ± 3.08 mm, respectively) and in LA group (26.2 ± 3.01, 19.5 ± 3.01 and 17.9 ± 2.9 mm, respectively). The most frequent drug-related adverse effects in dienogest group were vaginal bleeding and weight gain (64.5 and 10.8%, respectively) which were significantly higher than LA group (21.5 and 3.3%, respectively). While the most frequent drug-related adverse effects in LA group were hot flushes and vaginal dryness (46.3 and 15.7%, respectively) which were significantly higher than dienogest group (15.7 and 3.3%, respectively). CONCLUSION: Daily dienogest is as effective as depot LA for relieving endometriosis-associated pelvic pain, low back pain and dyspareunia. In addition, dienogest has acceptable safety, tolerability and lower incidence of hot flushes. Thus, it may offer an effective and well-tolerated treatment in endometriosis.

Interleukin-17 and leptin genes polymorphisms and their levels in relation to recurrent pregnancy loss in Egyptian females.

Recurrent pregnancy loss (RPL) is a common problem during early gestation. The aim of our study was to investigate the association of IL-17 F( rs763780), IL-17 A (rs2275913), and leptin (2548 G/A) gene polymorphisms with RPL in obese and lean Egyptian females, and to find out whether these gene polymorphisms affect the women's serum levels. One hundred and twenty patients with RPL and 120 fertile volunteers with no history of pregnancy loss were genotyped for leptin (2548 G/A), IL-17 A (rs2275913), and IL-17 F (rs763780) polymorphisms by RFLP. The serum level of IL-17 was measured by ELISA, while serum leptin level was measured by HPLC. We found that IL-17 F (rs763780) polymorphism was associated with a decreased risk of RPL in Egyptian females, and we also found that IL-17 A (rs2275913) and LEP (2548 G/A) SNP were associated with an increased risk of RPL. We also demonstrated that both the IL-17 and leptin levels were elevated in the women with RPL and in an obese subgroup within RPL in comparison to a lean one.

COX-2 gene promoter DNA methylation status in eutopic and ectopic endometrium of Egyptian women with endometriosis.

The pathophysiology of COX-2 expression in endometriosis is a matter of debate. The aim was to investigate the role of DNA methylation of the NF-IL6 site within the promoter of COX-2 gene in the pathogenesis of endometriosis. The endometrial tissues (ectopic and eutopic) were collected from 60 women with endometriosis and 30 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation-specific PCR. Quantitative real-time PCR (RT-PCR) was performed to measure COX-2 mRNA levels in endometrial tissues. We found significantly higher levels of COX-2 in ectopic endometriotic tissue compared with eutopic tissue. Also, we found that the frequencies of methylation status of the NF-IL6 site within the COX-2 promoter in the eutopic and ectopic endometrial tissues of endometriosis groups were significantly decreased in comparison to controls (P=0.002, P=0.000 respectively). Our study demonstrated that DNA hypomethylation of the NF-IL6 site within the promoter of COX-2 gene could be a key mechanism for its elevated expression in the eutopic and ectopic tissues of endometriosis.