Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

Background: An influence of gonadotropins (hCG) on the development of ovarian cancer has been discussed. Therefore, we quantified serum hCG levels in patients with benign and malignant ovarian tumors and the hCG expression in ovarian cancer tissue in order to analyze its relation to grade, stage, gonadotropin receptor (LH-R, FSH-R) expression and survival in ovarian cancer patients. Methods: Patients diagnosed and treated for ovarian tumors from 1990 to 2002 were included. Patient characteristics, histology including histological subtype, tumor stage, grading and follow-up data were available. Serum hCG concentration measurement was performed with ELISA technology, hCG tissue expression determined by immunohistochemistry. Results: HCG-positive sera were found in 26.7% of patients with benign and 67% of patients with malignant ovarian tumors. In addition, significantly higher hCG serum concentrations were observed in patients with malignant compared to benign ovarian tumors (p = 0.000). Ovarian cancer tissue was positive for hCG expression in 68%. We identified significant differences in hCG tissue expression related to tumor grade (p = 0.022) but no differences with regard to the histological subtype. In addition, mucinous ovarian carcinomas showed a significantly increased hCG expression at FIGO stage III compared to stage I (p = 0.018). We also found a positive correlation of hCG expression to LH-R expression, but not to FSH-R expression. There was no significant correlation between tissue hCG expression and overall ovarian cancer patient survival, but subgroup analysis revealed an increased 5-year survival in LH-R positive/FSH-R negative and hCG positive tumors (hCG positive 75.0% vs. hCG negative 50.5%). Conclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage. HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic value. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies

Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights

Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube