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目的探讨CDH1基因异常甲基化在上皮性卵巢癌发生发展中的作用及临床意义。方法对中国医科大学附属第一医院妇科、辽宁省肿瘤医院妇科1999年至2006年63例上皮性卵巢癌组织原发灶、41例相应的盆腹腔转移灶、10例癌旁卵巢组织及20例正常卵巢组织,采用甲基化特异性聚合酶链式反应(MSP)法检测CDH1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相应的盆腹腔转移灶中存在CDH1基因启动子区异常甲基化,发生率分别为28.6%、39.0%,显著高于正常卵巢组织(P<0.01)。10例癌旁卵巢组织中1例检测到CDH1基因启动子区甲基化,20例正常卵巢组织未检测到CDH1基因启动子区甲基化。CDH1基因启动子区甲基化的发生率在临床Ⅰ期和Ⅱ期显著低于Ⅲ期和Ⅳ期(P<0.05),在高分化癌中低于低分化癌(P<0.05)。结论CDH1基因启动子区异常甲基化与上皮性卵巢癌发生密切相关,并可能与上皮性卵巢癌转移、临床分期及分化程度有关。
Objective To investigate the role and clinical significance of abnormal methylation of CDH1 gene in the development of epithelial ovarian cancer. Methods From June 1999 to 2006, 63 cases of primary epithelial ovarian cancer, 41 cases of pelvic metastasis, 10 cases of paracancerous ovarian tissue and 20 cases of paracancerous ovarian cancer were collected from the First Affiliated Hospital of China Medical University and the Liaoning Provincial Tumor Hospital. In normal ovary tissue, methylation status of CDH1 gene promoter region was detected by methylation specific polymerase chain reaction (MSP). Results Aberrant methylation of the CDH1 gene promoter region was found in primary epithelial ovarian cancer tissues and corresponding pelvic metastases. The incidence rates of CDH1 gene promoter methylation were 28.6% and 39.0%, respectively, which were significantly higher than those in normal ovarian tissues (P <0.01). CDH1 gene promoter methylation was detected in 1 case of paracancer tissue and methylation of CDH1 gene promoter in 20 cases of normal ovarian tissue. The prevalence of CDH1 promoter methylation in stage Ⅰ and stage Ⅱ was significantly lower than that in stage Ⅲ and Ⅳ (P <0.05), but it was lower in well differentiated carcinoma than that in poorly differentiated carcinoma (P <0.05). Conclusion Aberrant methylation of CDH1 promoter region is closely related to the occurrence of epithelial ovarian cancer and may be related to the metastasis, clinical stage and differentiation of epithelial ovarian cancer.