Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis
Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis
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hMLH1表观遗传失活在卵巢子宫内膜异位症恶变中的作用
DOI：
10.1007/s00404-011-1922-x
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发表时间：
2012-01-01
影响因子：
2.6
通讯作者：
Ren, Fengyan
中科院分区：
文献类型：
--
作者：
Ren, Fang;Wang, Danbo;Ren, Fengyan
目的探讨hMLH1的表观遗传失活在卵巢子宫内膜异位症(EMS)恶变过程中的作用，探讨在位内膜hMLH1的表观失活与卵巢EM恶变的关系。方法采用激光捕获显微切割技术，对29例子宫内膜异位症相关卵巢癌(EAOC)、20例EMS和16例对照子宫内膜(CES)进行靶区组织切片。结果EAOC组肿瘤组织或异位内膜hMLH1启动子甲基化频率高于EMS组(P<0.05)，EAOC组在位内膜hMLH1启动子甲基化频率高于EMS组和CES组(P<；P<0.05)。此外，EAOC组在位内膜hMLH1蛋白表达低于EMS组和CES组(P<0.05)，hMLH1蛋白表达缺失与基因启动子甲基化显著相关。结论hMLH1的表观遗传失活是卵巢EMS恶变的早期事件。在位内膜hMLH1的表观遗传失活与异位内膜的表观遗传失活是同步的，子宫内膜异位内膜hMLH1的表观遗传失活可能成为早期诊断卵巢内膜恶变的分子工具。
PurposeTo investigate the role of epigenetic inactivation of hMLH1 during the malignant transformation of ovarian endometriosis (EMs), and to explore the relationship between the epigenetic inactivation of hMLH1 in eutopic endometria and the malignant transformation of ovarian EMs.MethodsThe target tissue from 29 cases of the endometriosis-associated ovarian carcinoma (EAOC) group, 20 cases of EMs group and 16 cases of control endometrium (CEs) group was obtained by laser capture microdissection (LCM). The methylation statue of hMLH1 promoter was determined by methylation-specific PCR (MSP) and the protein expression of hMLH1 was analysed by immunohistochemistry.ResultsThe frequency of promoter hypermethylation of hMLH1 in the neoplastic tissue or ectopic endometria of the EAOC group was higher than that of the EMs group (p< 0.05), and the frequency of promoter hypermethylation of hMLH1 in eutopic endometria of the EAOC group was higher than that of the EMs and CEs groups (p< 0.05). In addition, the protein expression of hMLH1 in eutopic endometria of the EAOC group was lower than that of the EMs and CEs group (p< 0.05), and absence of hMLH1 protein expression was significantly correlated with promoter hypermethylation of the gene.ConclusionsEpigenetic inactivation of hMLH1 was an early event in the malignant transformation of ovarian EMs. Epigenetic inactivation of hMLH1 in eutopic endometria was synchronous with that in ectopic endometria and the epigenetic inactivation of hMLH1 in eutopic endometria of EMs might be a potential molecular tool for early diagnosis of the malignant transformation of ovarian EMs.