上皮性卵巢肿瘤RASSF1A基因甲基化与蛋白表达的关系及意义

目的：检测上皮性卵巢肿瘤中RASSF1A基因启动子CpG岛的甲基化状态,并探讨基因异常甲基化与蛋白表达的关系及其意义。方法：运用甲基化特异性PCR（MSP）方法对62例上皮性卵巢癌、21例交界性囊腺瘤及30例良性囊腺瘤的RASSF1A基因启动子甲基化状态进行检测,免疫组化S-P法检测上述标本中RASSF1A蛋白表达,并结合肿瘤生物学行为进行分析。结果：上皮性卵巢癌组织、卵巢交界性囊腺瘤组织中RASSF1A基因启动子区甲基化率（58.06%、42.85%）显著高于卵巢良性囊腺瘤组织（13.33%）,差异有统计学意义（P〈0.05）。RASSF1A基因启动子区甲基化与上皮性卵巢癌的细胞分化程度和临床分期密切相关（P〈0.05）而与组织类型和患者年龄及绝经与否无相关性（P〉0.05）;RASSF1A基因甲基化与其蛋白表达下降一致。结论：卵巢癌组织中存在RASSF1A基因启动子CpG岛的异常甲基化,可能和该蛋白表达缺失的主要原因,是导致该基因失活的重要机制之一。

The relation between RASSF1A promoter CpG island methylation and RASSF1A protein expression in epithelial ovarian tumors

Objective：We detected the promoter methylation status of RASSF1A in various types of ovarian epithelial tumors,and evaluated its possible correlation with the expression of RASSF1A protein,and explored the mechanism in ovarian epithelial tumors.Methods： Promoter methylation of RASSF1A was detected using MSP（methylation-specifc polymerase chain reaction） in 62 cases of ovarian malignant epithelial tumor,21 cases of borderline cystadenoma and 30 cases of benign cystadenoma.The expression of RASSF1A was evaluated by immunohistochemistry S-P staining method.Results： RASSF1A promoter methylation rates in epithelial ovarian cancer and borderline cystadenoma was 58.06% and 42.85%,respectively,significantly higher than that in benign cystadenoma（13.33%）.The difference was significant（P0.05）.The frequency of hypermethylation of RASSF1A gene in epithelial ovarian cancer was not correlated with histological types,age and the menopause status（P0.05）;but it was strongly related to histologic cell types and clinical stage（P0.05）,there was a closely consistency between RASSF1A methylation and the decrease of protein expression.Conclusion： Methylation of RASSF1A genes is commonly seen in epithelial ovarian cancer.Methylation of RASSF1A promoter may play an important role in the down-regulation of RASSF1A expression.