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子宫内膜癌错配修复基因 的表达和启动子甲基化研究

【摘要】 【目的】 探讨子宫内膜癌组织中错配修复基因hMLH1 的表达和启动子甲基化状态与子宫内膜癌发生的关系。【方法】 应用免疫组化链霉素抗生物素- 过氧化物酶法(S-P法)和甲基化特异性聚合酶连反应(MSP)方法,检测37例子宫内膜癌组织和20例正常增生期子宫内膜组织中hMLH1蛋白的表达和启动子甲基化状态。【结果】 37例子宫内膜癌组织和20例正常增生期子宫内膜组织hMLH1基因蛋白表达分别为51.4%(19/37),85%(17/20);基因启动子甲基化分别为43.2%(16/37),15%(3/20)。发生甲基化的16例子宫内膜癌组织14例蛋白表达阴性,发生甲基化的3例正常增生期子宫内膜组织2例蛋白表达阴性。hMLH1蛋白表达与组织学分级(G1, G2, G3)有关,与肿瘤肌层浸润、淋巴结转移、国际妇产科协会(FIGO)分期和宫颈浸润无相关性,hMLH1的甲基化与上述临床病理因素均无相关性。【结论】 hMLH1基因启动子甲基化与其蛋白表达缺失密切相关,hMLH1基因在子宫内膜癌的发生过程中发挥重要作用。

  【关键词】 子宫内膜癌; hMLH1基因; 表达; 启动子甲基化

  Mismatch Repair Gene hMLH1 Expression and Promoter Methylation

  in Endometrial Carcinoma

  SHU Shan-rong1, KE Pei-qi1?鄢, LI Xiao-mao2, LI Mei-xiang3, WANG Li3, FEI Hui1

  (1. Department Of Gynecology and Obstetrics, The First Affiliated Hospital;

  2. Department Of Gynecology and Obstetrics, The Third Affiliated Hospital;

  3. Cancer Center, SUN Yat-sen University, Guangzhou 510630, China)

  Abstract: 【Objective】 To explore the correlation between the mismatch repair gene hMLH1 protein expression and promoter methylation with endometrial carcinoma. 【Methods】 The protein expression of hMLH1 and the status of promoter methylation were detected by immunohistochemistry and methylation specific PCR (MSP) in the tissues of endometrial carcinoma and normal proliferative endometrium. 【Results】 The protein expression rate of hMLH1 was 51.4% (19/37) in endometrial carcinoma and 85%(17/20) in normal proliferative endometrium, respectively. The DNA methylation rate was 43.2%(16/37) and 15%(3/20)in endometrial carcinoma and normal proliferative endometrium, respectively. The hMLH1 was not expressed in 14 of 16 methylated cases of endometrial carcinoma and 2 of 3 methylated cases of normal proliferative endometrium. The protein expression of hMLH1 was correlated with histological grade (G1, G2, G3) of endometrial carcinoma. No correlation was found between muscular layer invasion, lymph metastasis, FIGO stage and cervi

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