上皮性卵巢癌组织中RASSF1A和BRCA1及P16基因异常甲基化检测及其临床意义的研究

Promoter hypermethylation of RASSF1A,BRCA1 and p16 gene in epithelial ovarian cancer and its clinical significance

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 study the role of promoter hypermethylation of RASSF1A,BRCA1 and p16 gene in the course of tumorigenesis and progression of epithelial ovarian cancer. METHODS： Promoter hypermethylation of RASSF1A, BRCA1 and p16 gene was detected by methylation-specific PCP（MSP） in 63 epithelial ovarian cancer patients, corresponding 41 metastatic tissues of pelvic and abdomen cavity as well as 10 adjacent non-cancerous ovarian tissues. RESULTS： Promoter hypermethylation of RASSF1A, BRCA1 and p16 gene was detected in epithelial ovarian cancer tissues and metastatic sites, the frequency was 49. 2%, 25. 4% and 20. 6% in ovarian cancer tissues and 58.5% ,26.8,% and 22.0% in metastatic sites respectively,which was significantly higher than that in normal ovarian tissues, P〈0.05. The frequency of promoter hypermethylation of RASSF1A was significantly lower in epithelial ovarian cancers of stage Ⅰ and Ⅱ than that in stage Ⅲ and Ⅳ （Х^2 = 13. 018,P〈0. 000 1）, and so was that in both well and moderately differentiated cancers than that in poorly differentiated ones, Х^2=8.481,P=0.004;Х^2=8.195, P=0.004. CONCLUSIONS： Promoter hypermethylation of RASSF1A, BRCA1 and p16 gene correlates with tumorigenesis and progression of epithelial ovarian cancer. Promoter hypermethylation of RASSF1A is related to clinical stage and histopathological grade of epithelial ovarian cancer.