Zighelboim Israel, Goodfellow Paul J, Gao Feng, Gibb Randall K, Powell Matthew A, Rader Janet S, Mutch David G
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO 63110, USA.
J Clin Oncol. 2007 May 20;25(15):2042-8. doi: 10.1200/JCO.2006.08.2107.
Most 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.
Tumor 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.
MSI was identified in 147 cases (33%). MSI was associated with higher International Federation of Gynecology and Obstetrics (FIGO) grade (P < .0001). MSI+ tumors without MLH1 methylation were associated with younger age (P < .001). MSI was not associated with overall survival (OS; hazard ratio [HR], 1.011; 95% CI, 0.688 to 1.484; P = .96) or disease-free survival (DFS; HR 0.951; 95% CI, 0.554 to 1.635; P = .86). The combined MSI/MLH1 methylation status (treating MSI- as the reference) did not predict OS (MSI+/MLH1-U: HR, 0.62; 95% CI, 0.27 to 1.44; P = .26; MSI+/MLH1-M: HR, 0.95; 95% CI, 0.62 to 1.46; P = .82) or DFS (MSI+/MLH1-U: HR, 0.51; 95% CI, 0.22 to 1.19; P = .12; MSI+/MLH1-M: HR, 0.93; 95% CI, 0.62 to 1.40; P = .72).
MSI is not associated with survival in patients with endometrioid endometrial cancer.
大多数关于子宫内膜癌患者微卫星不稳定性（MSI）及其预后的研究纳入了多种组织学亚型。尽管如此，MSI几乎仅发生在子宫内膜样肿瘤中。MSI对子宫内膜癌患者预后的影响存在争议。我们试图确定在一大系列子宫内膜样腺癌患者中，MSI和MLH1甲基化是否与临床病理变量及生存结果相关。
前瞻性收集并分析了446例子宫内膜样腺癌患者的肿瘤样本、血液及临床病理数据。使用五个美国国立癌症研究所（NCI）共识小组标志物确定MSI，并通过联合亚硫酸氢盐限制分析（COBRA）确定MLH1启动子的甲基化状态。评估其与临床病理变量及生存结果的相关性。
147例（33%）患者检测到MSI。MSI与较高的国际妇产科联盟（FIGO）分级相关（P <.0001）。无MLH1甲基化的MSI+肿瘤与较年轻的年龄相关（P <.001）。MSI与总生存期（OS；风险比[HR]，1.011；95%置信区间[CI]，0.688至l.484；P =.96）或无病生存期（DFS；HR 0.951；95% CI，0.554至1.635；P =.86）无关。联合MSI/MLH1甲基化状态（将MSI-作为对照）不能预测OS（MSI+/MLH1-U：HR，0.62；95% CI，0.27至1.44；P =.26；MSI+/MLH1-M：HR，0.95；95% CI，0.62至1.46；P =.82）或DFS（MSI+/MLH1-U：HR，0.51；95% CI，0.22至1.19；P =.12；MSI+/MLH1-M：HR，0.93；95% CI，0.62至1.40；P =.72）。
MSI与子宫内膜样子宫内膜癌患者的生存无关。
