Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type

Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type
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DOI:
10.1200/jco.2006.08.2107
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发表时间:
2007-05-20
影响因子:
45.3
通讯作者:
Mutch, David G.
Mutch, David G.
中科院分区:
医学1区
文献类型:
--
作者:
Zighelboim, Israel;Goodfellow, Paul J.;Mutch, David G.

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大多数关于子宫内膜癌患者微卫星不稳定性(MSI)和预后的研究包括不同的组织学亚型。尽管如此,MSI几乎仅发生在类胶质瘤中。MSI对子宫内膜癌患者预后的影响存在争议。我们试图确定MSI和MLH1甲基化是否与临床病理变量和生存结果在一个大系列的子宫内膜癌的子宫内膜样癌type.Patients和MethodsTumor样本,血液和临床病理数据进行了前瞻性收集和分析446例子宫内膜样癌患者。使用五种国家癌症研究所(NCI)共有组标记物确定MSI,并通过联合亚硫酸氢盐限制性分析(COBRA)确定MLH1启动子的甲基化状态。与临床病理变量和生存outcomes.ResultsMSI的协会被确定在147例(33%)。MSI与国际妇产科联盟(FIGO)分级有关(P
PurposeMost studies of microsatellite instability (MSI) and outcomes in endometrial cancer patients have included varied histologic subtypes. Nonetheless, MSI occurs almost exclusively in endometrioid tumors. The impact of MSI on outcomes in patients with endometrial cancer is controversial. We sought to determine whether MSI and MLH1 methylation are associated with clinicopathologic variables and survival outcomes in a large series of patients with endometrial carcinomas of the endometrioid type.Patients and MethodsTumor samples, blood, and clinicopathologic data were prospectively collected and analyzed for 446 patients with endometrioid carcinomas. MSI was determined using five National Cancer Institute (NCI) consensus panel markers, and the methylation status of the MLH1 promoter was determined by combined bisulfite restriction analysis (COBRA). Associations with clinicopathologic variables and survival outcomes were evaluated.ResultsMSI was identified in 147 cases (33%). MSI was associated with higher International Federation of Gynecology and Obstetrics (FIGO) grade (P