RASSF2基因表观失活与卵巢内膜样腺癌的相关性

Investigation on the correlation between epigenetic inactivation of RASSF2 gene and ovarian endometrioid adenocarcinoma

目的:探讨RASSF2基因异常甲基化所导致的表观失活与卵巢内膜样腺癌的相关性。方法:甲基化特异性PCR技术及免疫组化技术检测46例卵巢内膜样腺癌组织RASSF2基因启动子区域的甲基化及组织中该基因的蛋白表达情况。结果:卵巢内膜样腺癌组织中RASSF2基因的甲基化发生率(24/46)及蛋白表达缺失发生率(25/46)均显著高于正常卵巢组织(0/10)及异位内膜组织(1/10),差异有显著的统计学意义(P<0.05)。内异症恶变相关卵巢内膜样腺癌组织中RASSF2基因甲基化发生率(7/11)与原发性卵巢内膜样腺癌组织中RASSF2基因甲基化发生率(17/35)无显著统计学差异(P>0.05)。RASSF2基因甲基化的组织中该基因蛋白表达缺失率96%(24/25)显著高于RASSF2基因非甲基化组织(2/41),RASSF2基因启动子区域异常高甲基化与其蛋白表达缺失具有相关性(P<0.05)。结论:RASSF2基因的表观失活可能在卵巢内膜样腺癌的发病机制中具有重要作用。

Objective： To investigate the correlation between epigenetic inactivation of RASSF2 gene by promoter hypermethylation and ovarian endometrioid adenocarcinoma. Methods： Methylation- specific PCR（ MSP） and immunohistochemistry were performed in 46 ovarian endometrioid adenocarcinoma samples to detect the methylation status and protein expression of RASSF2 gene,respectively. Results： In ovarian endometrioid adenocarcinoma tissue,methylation frequency（ 24 /46） and absence of protein expression of RASSF2（ 25 /46） were higher than that in the normal ovarian tissue and ectopic endometium（ P〈 0. 05）. There was no statistically significant difference between the methylation frequency of RASSF2 gene in malignant transformation of ovarian endometriosis associated ovarian endometrioid adenocarcinoma（ 7 /11） and in primary ovarian endometrioid adenocarcinoma（ 17 /35）（ P〈 0. 05）. The absence of protein expression of RASSF2 in the RASSF2 methylation tissue（ 24 /25） was significantly higher than in the RASSF2 unmethylation tissue（ 2 /41）. Absence of protein expression of RASSF2 was significantly correlated with the hypermethylation of the gene. Conclusion： Epigenetic inactivation of RASSF2 by promoter hypermethylation may be associated with the pathogenesis of ovarian endometrioid adenocarcinoma.