Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Am J Surg Pathol. 2011 Dec;35(12):1902-5. doi: 10.1097/PAS.0b013e318237c6ab.
Lynch syndrome accounts for approximately 3% of newly diagnosed colorectal cancers and is caused by germline defects in DNA mismatch repair genes. Screening of patients for Lynch syndrome can be done by immunohistochemical staining for a panel of mismatch repair proteins and/or DNA testing for microsatellite instability. We describe a unique "null" immunophenotype in a Lynch syndrome associated colon cancer in a 71-year-old woman who also had a personal history of ureteral cancer and a strong family history of various malignancies. Immunohistochemical stains for MLH1, MSH2, PMS2, and MSH6 were completely negative in the tumor cells, with positive staining in stromal and inflammatory cells. Mutation analysis using peripheral blood showed a germline G587R mutation in the MSH2 gene. Further testing revealed the tumor to be positive for MLH1 promoter hypermethylation. Normal colonic mucosa adjacent to the tumor was negative for MLH1 promoter methylation. The lack of immunostaining for any of the 4 DNA mismatch repair proteins in this extremely unusual case was, therefore, related to a germline MSH2 mutation and somatic MLH1 promoter hypermethylation.
林奇综合征约占新发结直肠癌的 3%，是由 DNA 错配修复基因的种系缺陷引起的。林奇综合征患者的筛查可通过免疫组化染色一组错配修复蛋白和/或微卫星不稳定性的 DNA 检测来完成。我们描述了一位 71 岁女性林奇综合征相关结肠癌的独特“缺失”免疫表型，该患者还患有输尿管癌个人史和多种恶性肿瘤的强烈家族史。肿瘤细胞中 MLH1、MSH2、PMS2 和 MSH6 的免疫组化染色完全为阴性，而间质和炎症细胞呈阳性染色。外周血突变分析显示 MSH2 基因存在种系 G587R 突变。进一步的检测显示肿瘤 MLH1 启动子呈高甲基化阳性。肿瘤旁正常结肠黏膜 MLH1 启动子甲基化阴性。在这种极其罕见的情况下，4 种 DNA 错配修复蛋白中的任何一种免疫染色缺失，因此与种系 MSH2 突变和体细胞 MLH1 启动子高甲基化有关。
