Kageyama Satoko, Ota Masayuki, Aihara Takanori, Nakama Kaito, Ikeda Jun-Ichiro
Department of Diagnostic Pathology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-Ku, Chiba, Japan.
Department of Pathology, Chiba University Hospital, 1-8-1 Inohana, Chuo-Ku, Chiba, Japan.
Virchows Arch. 2025 Sep 2. doi: 10.1007/s00428-025-04232-0.
Immunohistochemistry for mismatch repair (MMR) proteins is important for evaluating the molecular background of MMR-deficient tumors, including those with Lynch syndrome (LS). The four major MMR proteins function as heterodimers (MLH1/PMS2 and MSH2/MSH6), and usually only one of the MMR subsystems is impaired. However, rare cases of concurrent immunohistochemical loss of all four MMR proteins, termed "null" phenotype, have been reported. We present the first reported case of small bowel adenocarcinoma (SBA) showing a null-phenotype. A 62-year-old man developed jejunal cancer. Immunohistochemical analysis showed complete loss of all four MMR proteins in the entire tumor. Genetic testing revealed LS with a germline pathogenic variant in MSH2, and somatic mutations in MSH2 and MLH1 were also detected. No BRAF V600E mutation was found. Combined with comprehensive cancer genomic profiling, this report provides insight into an exceptional MMR-deficient tumor and SBA, a relatively rare disease given its surface area.
错配修复（MMR）蛋白的免疫组织化学检测对于评估MMR缺陷型肿瘤的分子背景非常重要，包括那些患有林奇综合征（LS）的肿瘤。四种主要的MMR蛋白以异二聚体形式发挥作用（MLH1/PMS2和MSH2/MSH6），通常只有一个MMR子系统受损。然而，已经报道了罕见的所有四种MMR蛋白同时出现免疫组织化学缺失的情况，称为“无效”表型。我们报告了首例显示无效表型的小肠腺癌（SBA）病例。一名62岁男性患空肠癌。免疫组织化学分析显示整个肿瘤中所有四种MMR蛋白完全缺失。基因检测发现LS，其MSH2存在种系致病变异，同时还检测到MSH2和MLH1的体细胞突变。未发现BRAF V600E突变。结合全面的癌症基因组分析，本报告为一种特殊的MMR缺陷型肿瘤和SBA（鉴于其表面积，这是一种相对罕见的疾病）提供了见解。
