Chen Huai-zeng, Ye Da-feng, Xie Xing, Hu Min, Lu Wei-guo
Department of Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Aug;25(4):457-61.
To investigate the role of hMLH1 promoter hypermethylation and microsatellite instability (MSI) in the development of ovarian mucinous tumors.
One hundred and seven of paraffin-embedded specimens of ovarian mucinous tumors (malignant 49, borderline 35, and benign 23) were collected from Women's Hospital, School of Medicine, Zhejiang University from 1995 to 2001. The assessment of MSI was based on the use of a panel of six microsatellite markers (BAT-25, BAT-26, BAT-40, D5S346, D17S250, and D2S123) by polymerase chain reaction (PCR). Hypermethylation of hMLH1 promoter region was detected using restriction cut analysis.
4.3% (1/23), 14.3% (5/35), and 36.7% (18/49) of benign tumors, borderline tumors, and malignant tumors respectively displayed hypermethylation of the hMLH1 promoter. The hMLH1 promoter hypermethylation rate of malignant group was significantly higher than that of borderline and benign group (P = 0.023, 0.004), but no significant difference between the borderline group and the benign group (P = 0.438); 4.3% (1/23), 8.6% (3/35), and 16.3% (8.49) of benign tumors, borderline tumors, and malignant tumors showed MSI positive phenotype. But there were no significant differences each other in the MSI positive phenotype rate; 75% (9/12) MSI positive phenotype ovarian mucinous tumors were hypermethylated at hMLH1 promoter, while the MSI-phenotype tumors were unmethylated in 84.2% (80.95) of cases. There was significant correlation between MSI positive phenotype and hMLH1 promoter hypermethylation (P = 0.000).
In ovarian mucinous tumors, malignant, borderline, and benign tumors exist hMLH1 promoter hypermethylation. Hypermethylation of hMLH1 promoter results MSI in ovarian mucinous tumors. Methylation of hMLH1 promoter and MSI may be involved in the carcinogenesis of ovarian mucinous cancer.
探讨hMLH1启动子高甲基化及微卫星不稳定性（MSI）在卵巢黏液性肿瘤发生发展中的作用。
收集1995年至2001年浙江大学医学院附属妇产科医院107例卵巢黏液性肿瘤石蜡包埋标本（恶性49例、交界性35例、良性23例）。采用聚合酶链反应（PCR），利用一组6个微卫星标记（BAT - 25、BAT - 26、BAT - 40、D5S346、D17S250和D2S123）评估MSI。采用酶切分析检测hMLH1启动子区域的高甲基化。
良性肿瘤、交界性肿瘤和恶性肿瘤中hMLH1启动子高甲基化率分别为4.3%（1/23）、14.3%（5/35）和36.7%（18/49）。恶性组hMLH1启动子高甲基化率显著高于交界性组和良性组（P = 0.023，0.004），但交界性组与良性组之间差异无统计学意义（P = 0.438）；良性肿瘤、交界性肿瘤和恶性肿瘤中MSI阳性表型分别为4.3%（1/23）、8.6%（3/35）和16.3%（8/49）。但MSI阳性表型率之间差异无统计学意义；MSI阳性表型的卵巢黏液性肿瘤中75%（9/12）hMLH1启动子高甲基化，而MSI阴性表型肿瘤84.2%（80/95）未甲基化。MSI阳性表型与hMLH1启动子高甲基化之间存在显著相关性（P = 0.000）。
在卵巢黏液性肿瘤中，恶性、交界性和良性肿瘤均存在hMLH1启动子高甲基化。hMLH1启动子高甲基化导致卵巢黏液性肿瘤发生MSI。hMLH1启动子甲基化和MSI可能参与卵巢黏液性癌的发生。
