Christensen Mariann, Katballe Niels, Wikman Friedrik, Primdahl Hanne, Sørensen Flemming B, Laurberg Søren, Ørntoft Torben F
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Cancer. 2002 Dec 1;95(11):2422-30. doi: 10.1002/cncr.10979.
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.
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.
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.
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.
DNA错配修复基因MSH2、MLH1等的种系突变与遗传性非息肉病性结直肠癌（HNPCC）相关。由于测序成本高昂，需要更便宜的筛查方法来识别HNPCC病例。理想情况下，这些方法应具有高灵敏度，能识别所有突变病例且假阳性病例不多。
将测序与微卫星分析及免疫组织化学进行比较，以检测错配修复蛋白的有无。在本研究中，作者检查了42例结直肠癌患者，其中11例符合阿姆斯特丹标准，31例疑似属于HNPCC家族。35例患者接受了微卫星分析，40例进行了免疫组织化学染色，31例患者对MLH1和MSH2基因进行了测序。
92%的种系突变患者通过免疫组织化学或微卫星不稳定性检测到，这表明这些方法的联合应用可能适用于HNPCC筛查。73%的肿瘤存在微卫星不稳定性和异常免疫组织化学染色。74%的肿瘤三种方法结果一致。
作者建议免疫组织化学应与微卫星分析联合使用，对疑似HNPCC患者进行预筛查，以选择需要对MLH1和MSH2错配修复基因进行测序的病例。
