Clinicopathological and Molecular Analyses for Possible Correlation between Infertility Therapy and Development of Ocarian Cancer

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Possible relationship between infertility therapy and development of ovarian cancer has recently received much attention, and there have been case reports of ovarian carcinoma which occurred during ovulation-induction using gonadotropic agents. The aim of this research project is to clarify the clinicopathological characteristics of ovarian cancer in this setting, and to examine if gonadotropins affect ovarian cancer or ovarian surface epithelium, the histogenetic origin of epithelial ovarian carcinoma.Analysis of our 6 cases and review of the literature revealed that ovarian carcinomas during or after ovulation-induction therapy are classified into 2 types : one is serous type carcinoma or LMP tumor. Clinically, such tumors suddenly appeared and are frequently associated with intraperitoneal metastases. Early detection of serous carcinoma is difficult even during the infertility treatment. Another type is clear cell or endometrioid carcinoma arising in endometriotic cyst. Early detect … More ion of this type carcinoma is possible by careful followup using transvaginal ultrasonography and MRI.Our study demonstrated that ovarian surface epithelium (OSE) is immunoreactive for LH/hCG receptors. In the primary culture system of OSE, these cells exhibited specific binding capacity for hCG, and expressed mRNA of LH/hCG receptor gene. hCG not only enhanced the proliferative activity, but also inhibited apoptosis induced by serum-deprivation in OSE cells. Signal transduction of apoptotic inhibition by hCG occurred via up-regulation of insulin-like growth factor-i (IGF-1). These results suggest that gonadotropins are presumably involved in the behavior of OSE such as repair of the ovarian surface after ovulation.An approximately half of ovarian carcinomas expressed LH/hCG receptor at both mRNA and protein levels. In ovarian cancer cell line (OVCAR3) expressing LH/hCG receptors, hCG inhibited cisplatin-induced apoptosis via up-regulation of IGE-1. Accordingly, gonadotropins may also play an important role in biological behavior and/or chemoresistance of ovarian cancer. In conclusion, our studies suggest the causal relationship between infertility therapy and ovarian cancer. Less