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

不孕症治疗与卵巢癌发生之间的可能关系最近受到了广泛关注，并且已有使用促性腺激素药物诱导排卵期间发生卵巢癌的病例报告。本研究的目的是阐明卵巢癌的临床病理学特征，并检查促性腺激素是否影响卵巢癌或卵巢表面上皮，上皮性卵巢癌的组织发生学起源。通过对我们6例病例的分析和文献回顾，发现促排卵治疗期间或之后的卵巢癌可分为2种类型：一种是浆液性癌或LMP肿瘤。临床上，这种肿瘤突然出现，并经常与腹膜内转移有关。即使在不孕症治疗期间，早期发现浆液性癌也很困难。另一种类型是透明细胞癌或类透明细胞癌，起源于类透明细胞囊肿。早期发现 ...更多信息 我们的研究表明，卵巢表面上皮（OSE）对LH/hCG受体呈免疫反应性。在OSE原代培养体系中，这些细胞对hCG具有特异性结合能力，并表达LH/hCG受体基因mRNA。hCG不仅能增强OSE细胞的增殖活性，而且能抑制血清剥夺诱导的OSE细胞凋亡。hCG通过上调胰岛素样生长因子-I（IGF-1）抑制细胞凋亡的信号转导。这些结果表明促性腺激素可能参与OSE的行为，如排卵后卵巢表面的修复。大约一半的卵巢癌在mRNA和蛋白水平上表达LH/hCG受体。在表达LH/hCG受体的卵巢癌细胞系（OVCAR 3）中，hCG通过上调IGE-1抑制顺铂诱导的凋亡。因此，促性腺激素也可能在卵巢癌的生物学行为和/或化疗耐药性中发挥重要作用。总之，我们的研究表明不孕治疗和卵巢癌之间存在因果关系。少

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