Microsatellite instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer
Microsatellite instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer
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DOI：
10.1038/labinvest.3780262
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发表时间：
2001-04-01
影响因子：
5
通讯作者：
Lindblom, A
中科院分区：
文献类型：
--
作者：
Salahshor, S;Koelble, K;Lindblom, A
错配修复基因产物的免疫组化表达分析已被建议用于预测遗传性非息肉病性结直肠癌（HNPCC）的癌症家族中的携带者状态和选择散发性结直肠癌中的微卫星不稳定性（MSI）阳性肿瘤。在这项研究中，我们的目的是评估hMSH2和hMLH1免疫组化在家族性和散发性结直肠癌。我们发现，免疫组化使我们能够确定hMSH2的生殖系突变的患者和许多hMLH1的生殖系突变的病例。然而，一些错义突变和截短突变可能会被遗漏。此外，hMLH1启动子甲基化，通常发生在家族性和散发性MSI阳性结直肠癌，可以复杂的免疫组化表达分析的解释。我们的研究结果表明，免疫组化不能取代MSI检测来预测HNPCC携带者状态或识别MSI阳性的散发性结直肠癌。
Immunohistochemical expression analysis of mismatch repair gene products has been suggested for the prediction of hereditary nonpolyposis colorectal cancer (HNPCC) carrier status in cancer families and the selection of microsatellite instability (MSI)-positive tumors in sporadic colorectal cancer. In this study, we aimed to evaluate hMSH2 and hMLH1 immunohistochemistry in familial and sporadic colorectal cancer. We found that immunohistochemistry allowed us to identify patients with germline mutations in hMSH2 and many cases with germline mutations in hMLH1. However, some missense and truncating mutations may be missed. In addition, hMLH1 promoter methylation, commonly occurring in familial and sporadic MSI-positive colorectal cancer, can complicate the interpretation of immunohistochemical expression analyses. Our results suggest that immunohistochemistry cannot replace testing for MSI to predict HNPCC carrier status or identify MSI-positive sporadic colorectal cancer.