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Abstract：
Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.
摘要：
尽管用于错配修复（MMR）蛋白（MMRIHC）的免疫组织化学（IHC）用于鉴定DNAMMR状态，在日本,使用MMRIHC和BRAFV600E突变基因检测相结合的方法对所有结直肠癌(CRC)患者进行的普遍筛查有限.本研究旨在更好地了解CRC的组织病理学特征，表现出缺陷性错配修复（dMMR）和BRAFV600E突变。从滨松大学医院接受手术切除的651例CRC患者（滨松，日本)在2016年8月至2022年3月期间用于评估MMR状态，其通过染色4种MMR蛋白(MLH1、MSH2、PMS2和MSH6)的表达来确定。通过Sanger测序额外评估所有dMMR肿瘤的BRAFV600突变状态。患者临床特征（年龄，性别,肿瘤位置,尺寸,和肿瘤病理）然后使用其dMMR和BRAFV600突变状态进行分类。在651例CRC患者中，58例携带dMMR的肿瘤，其中52例缺乏MLH1（dMLH1）。有趣的是,分析的所有16例髓样癌都显示出与dMLH1和BRAFV600E突变同时存在相对应的特征(P=.01).这些结果表明，结直肠髓样癌可以根据其具有BRAFV600E突变和表现出dMLH1表达的独特特征来诊断。
