Antibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing
Antibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing
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DOI：
10.1002/cncr.10979
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发表时间：
2002-12-01
期刊：
影响因子：
6.2
通讯作者：
Orntoft, TF
中科院分区：
文献类型：
--
作者：
Christensen, M;Katballe, N;Orntoft, TF
背景资料。DNA错配修复基因MSH2、MLH1和其他基因的种系突变与遗传性非息肉病性结直肠癌(HNPCC)有关。由于测序成本高，需要更便宜的筛查方法来识别HNPCC病例。理想情况下，这些方法应该具有很高的灵敏度，并在不出现太多假阳性的情况下识别所有突变病例。方法：将测序结果与微卫星分析和免疫组织化学进行比较，以检测错配修复蛋白的存在或不存在。在目前的研究中，作者检查了42名结直肠癌患者，其中11人符合阿姆斯特丹标准，31人怀疑属于HNPCC家族。35例患者进行了微卫星分析，40例患者进行了免疫组织化学染色，31例患者同时进行了MLH1和MSH2基因测序。结果：92%的生殖系突变患者通过免疫组织化学或微卫星不稳定性检测，表明这两种方法的结合可能适合于HNPCC的筛查。73%的肿瘤存在微卫星不稳定性和免疫组织化学染色异常。结论免疫组织化学结合微卫星分析对疑似HNPCC患者进行预筛查，可用于MLH1和MSH2错配修复基因测序阳性病例的筛选。(C)2002年美国癌症协会。
BACKGROUND. Germline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high sensitivity and identify all mutated cases without too many false-positive cases.METHODS. Sequencing was compared with microsatellite analysis and immunohistochemistry to detect the presence or absence of the mismatch repair proteins. In the current study, the authors examined 42 patients with colorectal carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty-five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced.RESULTS. Ninety-two percent of patients with germ line mutations were detected by either immunohistochemistry or microsatellite instability, indicating that a combination of these methods may be suitable for HNPCC screening. Microsatellite instability and abnormal immunohistochemical staining were found in 73% of the tumors. Concordance among the three methods was found in 74% of the tumors.CONCLUSIONS. The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated. (C) 2002 American Cancer Society.