Clinical performance of original and revised Bethesda guidelines for the identification of MSH2/MLH1 gene carriers in patients with newly diagnosed colorectal cancer:: Proposal of a new and simpler set of recommendations
Clinical performance of original and revised Bethesda guidelines for the identification of MSH2/MLH1 gene carriers in patients with newly diagnosed colorectal cancer:: Proposal of a new and simpler set of recommendations
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DOI：
10.1111/j.1572-0241.2006.00522.x
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发表时间：
2006-05-01
影响因子：
9.8
通讯作者：
Bujanda, Luis
中科院分区：
文献类型：
--
作者：
Rodriguez-Moranta, Francisco;Castells, Antoni;Bujanda, Luis
确定谁应该接受遗传性非息肉病性结直肠癌（HNPCC）基因检测的个人是一个关键和困难的问题。为此，美国国家癌症研究所（National Cancer Institute）提出了一系列建议，即最近修订的Bethesda指南。目的：比较原指南和修订后的Bethesda指南检测结直肠癌患者MSH 2/MLH 1基因携带者的临床表现。共有1,222例新诊断的结直肠癌患者被纳入EPICOLON研究，这是一项前瞻性、多中心、旨在确定西班牙HNPCC发病率的全国流行病学调查（JAMA 2005; 293：1986-1994）。针对MSH 2/MLH 1生殖系突变的存在，评估了原始和修订的Bethesda指南的性能特征。结果：原Bethesda指南和修订Bethesda指南在敏感性方面是等效的（100% vs 100%; ns），特异性（98.1% vs 97.9%; ns）和总体准确性（98.1% vs 97.9%; ns），以及阳性（25.8% vs 24.2%）和阴性预测值（100% vs 100%）。最具鉴别力的个体变量是标准1（即，符合Amsterdam标准; RR = 34.14; 95%CI = 6.85-170.16; p < 0.001）和2号（即，患有两种HNPC相关肿瘤的个体; RR = 35.63; 95%CI = 4.83-262.6; p < 0.001）和修订指南的标准1（即，50岁以下诊断的结直肠癌; RR = 29.34; 95%CI = 3.81-225.96; p = 0.001）。这三个标准的总和在敏感性（100%）和阴性预测值（100%）方面与Bethesda指南相当，但在特异性方面上级修订标准（98.5%; p < 0.05），总体准确度（98.5%; p < 0.05），阳性预测值（30.8%）。原始和修订后的贝塞斯达指南是等效的，新诊断结直肠癌患者MSH 2/MLH 1基因突变携带者的高效鉴别标准。一套新的建议，结合其一些个别标准，可能在有效性方面提供更多的好处。
Identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is a critical and difficult issue. For this purpose, the National Cancer Institute outlined a set of recommendations, the Bethesda guidelines, which have recently been revised.OBJECTIVE: To compare the clinical performance of original and revised Bethesda guidelines for the detection of MSH2/MLH1 gene carriers in patients with colorectal cancer.METHODS: A total of 1,222 patients with newly diagnosed colorectal cancer were included in the EPICOLON study, a prospective, multicenter, nationwide epidemiology survey aimed at establishing the incidence of HNPCC in Spain (JAMA 2005; 293:1986-1994). Performance characteristics of the original and revised Bethesda guidelines were assessed with respect to the presence of MSH2/MLH1 germline mutations. Logistic regression analysis was performed to establish the most effective strategy.RESULTS: Original or revised Bethesda guidelines were equivalent strategies in terms of sensitivity (100% vs 100%; ns), specificity (98.1% vs 97.9%; ns), and overall accuracy (98.1% vs 97.9%; ns), as well as positive (25.8% vs 24.2%) and negative predictive values (100% vs 100%). The most discriminating individual variables were criteria number 1 (i.e., fulfillment of the Amsterdam criteria; RR = 34.14; 95% CI = 6.85-170.16; p < 0.001) and number 2 (i.e., individuals with two HNPCC-related neoplasms; RR = 35.63; 95% CI = 4.83-262.6; p < 0.001) of the original guidelines, and criterion number 1 of the revised guidelines (i.e., colorectal cancer diagnosed under 50 yr of age; RR = 29.34; 95% CI = 3.81-225.96; p = 0.001). The aggregation of these three criteria was equivalent to both Bethesda guidelines in terms of sensitivity (100%) and negative predictive value (100%), but superior to the revised criteria regarding specificity (98.5%; p < 0.05), overall accuracy (98.5%; p < 0.05), and positive predictive value (30.8%).CONCLUSIONS: Original and revised Bethesda guidelines are equivalent, highly effective criteria for the identification of MSH2/MLH1 gene mutation carriers in patients with newly diagnosed colorectal cancer. A new set of recommendations, based on a combination of some of their individual criteria, may provide additional advantages in terms of effectiveness.