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

不孕症治疗与 Ocarian 癌发展之间可能相关性的临床病理学和分子分析

基本信息

批准号：
09470358
负责人：
KONISHI Ikuo
金额：
$ 6.85万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

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

不孕治疗与卵巢癌发展之间可能的关系最近受到广泛关注，并且已有使用促性腺激素诱导排卵期间发生卵巢癌的病例报告。本研究项目的目的是阐明卵巢癌的临床病理特征。在这种情况下，并检查促性腺激素是否影响卵巢癌或卵巢表面上皮，即上皮性卵巢癌的组织遗传学起源。分析我们对6例病例进行回顾性分析，发现促排卵治疗期间或之后的卵巢癌分为两种类型：一种是浆液型癌或LMP肿瘤，临床上此类肿瘤突然出现，且常伴有早期腹膜内转移。即使在不孕症治疗期间，浆液性癌的检测也很困难。另一种类型是子宫内膜异位囊肿中出现的透明细胞癌或子宫内膜样癌，通过仔细随访可以早期检测到这种类型的癌。我们的研究表明，卵巢表面上皮 (OSE) 对 LH/hCG 受体具有免疫反应性，在 OSE 的原代培养系统中，这些细胞表现出对 hCG 的特异性结合能力，并表达 LH/hCG 受体基因的 mRNA。 hCG 不仅增强增殖活性，而且还通过上调抑制血清剥夺诱导的 OSE 细胞凋亡。这些结果表明，促性腺激素可能参与 OSE 的行为，例如排卵后卵巢表面的修复。大约一半的卵巢癌在两者中表达 LH/hCG 受体。在表达 LH/hCG 受体的卵巢癌细胞系 (OVCAR3) 中，hCG 通过上调 IGE-1 抑制顺铂诱导的细胞凋亡。促性腺激素也可能在卵巢癌的生物学行为和/或化疗耐药中发挥重要作用。总之，我们的研究表明不孕症治疗与卵巢癌之间的因果关系。