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目的:探讨RASSF1A、BRCA1和p16基因异常甲基化在上皮性卵巢癌发生及发展中的作用。方法:采用甲基化特异性PCR法检测63例上皮性卵巢癌组织和相应的41例盆腹腔转移灶及10例癌旁卵巢组织中RASSF1A、BRCA1和p16基因启动子区甲基化状态。结果:上皮性卵巢癌组织原发灶及转移灶中RASSF1A、BRCA1和p16基因启动子区甲基化发生率分别为49·2%、25·4%、20·6%及58·5%、26·8%、22·0%,均显著高于正常卵巢组织中的发生率,P值均<0·05。RASSF1A基因启动子区异常甲基化的发生率在临床Ⅰ、Ⅱ期显著低于Ⅲ、Ⅳ期,χ2=13·018,P<0·0001;在高、中分化癌的发生率均显著低于低分化癌,χ2=8·481,P=0·004;χ2=8·195,P=0·004。结论:RASSF1A、BRCA1和p16基因异常甲基化与上皮性卵巢癌的发生及发展相关,RASSF1A基因异常甲基化与上皮性卵巢癌临床分期及分化程度相关。
Objective: To investigate the role of aberrant methylation of RASSF1A, BRCA1 and p16 genes in the development and progression of epithelial ovarian cancer. Methods: The methylation status of RASSF1A, BRCA1 and p16 genes in 63 cases of epithelial ovarian cancer, 41 cases of pelvic peritoneal metastases and 10 cases of para-cancerous ovarian tissues were detected by methylation-specific PCR. Results: The methylation rates of RASSF1A, BRCA1 and p16 promoter region in epithelial ovarian cancer tissue were 49.2%, 25.4%, 20.6% and 58.5% respectively, 26.8% and 22.0% respectively, which were significantly higher than those in normal ovarian tissue (P <0.05). The incidence of abnormal methylation of promoter region of RASSF1A gene in stage Ⅰ and Ⅱ was significantly lower than that in stage Ⅲ and Ⅳ (χ2 = 13.018, P <0.0001). The incidence of high and moderately differentiated carcinoma was significantly lower In poorly differentiated carcinoma, χ2 = 8 · 481, P = 0.004; χ2 = 8 · 195, P = 0.004. Conclusion: Aberrant methylation of RASSF1A, BRCA1 and p16 genes is associated with the occurrence and development of epithelial ovarian cancer. The abnormal methylation of RASSF1A gene is associated with the clinical stage and differentiation of epithelial ovarian cancer.