Validation Microsatellite Path Score in a Population-Based Cohort of Patients With Colorectal Cancer
Validation Microsatellite Path Score in a Population-Based Cohort of Patients With Colorectal Cancer
复制标题
DOI：
10.1200/jco.2010.34.3947
复制
发表时间：
2011-09-01
影响因子：
45.3
通讯作者：
Andreu, Montserrat
中科院分区：
文献类型：
--
作者：
Bessa, Xavier;Alenda, Cristina;Andreu, Montserrat
贝塞斯达指南用于识别Lynch综合征的风险患者。然而，获得个人和家族肿瘤数据有时可能很困难。微卫星路径评分（MsPath）是一种基于年龄、肿瘤位置和病理特征的病理评分，已被开发用于有效预测具有DNA错配修复（MMR）缺陷的结直肠癌。然而，MsPath模型的性能在一个独立的，基于人群的结直肠癌（CRC）populationis unknown.Patients and MethodsWe分析了所有CRC患者，无论年龄，个人或家族史，和肿瘤特征从EPICOLON研究，一个独立的，前瞻性的，多中心的，基于人群的队列（N = 1,222）。所有患者均接受肿瘤微卫星不稳定性（MSI）分析和MLH 1/MSH 2免疫染色，MMR患者接受肿瘤BRAF突变分析和MLH 1/MSH 2生殖细胞检测。结果MsPath评分预测高MSI的敏感性、特异性和阳性预测值（PPV）为92.8%，推荐的MsPath临界值>1.0（95% CI，86.9至98.3）、64.1%（95% CI，61.1至66.8）和15.8%（95% CI，12.2至18.6）。MsPath评分识别MLH 1/MSH 2基因携带者的灵敏度、特异性和PPV分别为81.8%（95%CI，59.0 - 99.8）、60.6%（95%CI，57.8 - 63.4）和1.9%（95%CI，0.7 - 3.1）。MsPath评分的应用，导致两个（18%）的11个突变载体被错过，致病性生殖系MSH 2 mutations.ConclusionIn一般nonselected人口，MsPath评分准确预测的概率轴承MSI高CRC，但它是不够准确的选择使用的患者在设置林奇综合征的MLH 1/MSH 2突变检测。临床肿瘤学杂志29：3374-3380。(C)2011年美国临床肿瘤学会
PurposeBethesda guidelines are used to recognize patients at risk for Lynch syndrome. However, obtaining personal and familial tumor data can sometimes be difficult. The Microsatellite Path Score (MsPath), a pathological score, based on age, tumor location, and pathologic features, has been developed to effectively predict colorectal cancer with DNA mismatch repair (MMR) deficiencies. However, the MsPath model's performance in an unselected, population-based colorectal cancer (CRC) population is unknown.Patients and MethodsWe analyzed all patients with CRC regardless of age, personal or family history, and tumor characteristics from the EPICOLON study, an independent, prospective, multicenter, population-based cohort (N = 1,222). All patients underwent tumor microsatellite instability (MSI) analysis and immunostaining for MLH1/MSH2, and those with MMR underwent tumor BRAF mutation analysis and MLH1/MSH2 germline testing. All the pathologic features were centralized and evaluated blinded to the MMR status.ResultsMsPath score for prediction of having MSI high, with the recommended MsPath cutoff score >1.0, had a sensitivity, specificity, and positive predictive value (PPV) of 92.8% (95% CI, 86.9 to 98.3), 64.1% (95% CI, 61.1 to 66.8), and 15.8% (95% CI, 12.2 to 18.6), respectively. MsPath score had a sensitivity, specificity, and PPV of 81.8% (95% CI, 59.0 to 99.8), 60.6% (95% CI, 57.8 to 63.4), and 1.9% (95% CI, 0.7 to 3.1), respectively, for the identification of MLH1/MSH2 gene carriers. Application of the MsPath score, resulted in two (18%) of 11 mutation carriers being missed, both pathogenic germline MSH2 mutations.ConclusionIn the general nonselected population, the MsPath score accurately predicted the probability of bearing a MSI high CRC, but it was insufficiently accurate to use for the selection of patients warranting MLH1/MSH2 mutation testing in the setting of Lynch syndrome. J Clin Oncol 29:3374-3380. (C) 2011 by American Society of Clinical Oncology