Chikatani Kenichi, Chika Noriyasu, Tanabe Noriko, Mori Yoshiko, Suzuki Okihide, Matsuyama Takatoshi, Ishibashi Keiichiro, Eguchi Hidetaka, Okazaki Yasushi, Yamaguchi Tatsuro, Ishida Hideyuki
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
Department of Clinical Genetics, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
J Anus Rectum Colon. 2025 Jan 25;9(1):145-155. doi: 10.23922/jarc.2024-092. eCollection 2025.
Mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC) have been largely categorized into three subtypes: methylated, Lynch syndrome (LS)-associated, and Lynch-like syndrome (LLS)-associated. No studies have examined the prevalence and subtypes of synchronously diagnosed dMMR CRCs in detail. Therefore, this study aimed to examine the frequency and molecular characteristics of the dMMR status among multiple synchronous CRCs to clarify the clinical significance of identifying patients with such tumors.
Immunohistochemistry (IHC) of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed for surgically and endoscopically resected (in conjunction with surgical resection) lesions from consecutive patients with initially diagnosed multiple synchronous CRCs between July 2014 and June 2020. When necessary, -methylation analysis and testing of germline and somatic MMR genes were performed.
In total, 133 patients (33 females) had 309 lesions. The combinations of synchronous tumor sites were the left-sided colon/rectum only (n=67, 50.4%), both the right-sided colon and left-sided colon/rectum (n=42, 31.6%), and the right-sided colon only (n=24, 18.0%). IHC showed a loss of expression of at least one MMR protein in 10 (7.5%) of 133 patients and 17 (5.5%) of 309 lesions. Molecular analysis revealed that these 10 patients were categorized as having -methylated (n=5, 3.8% of all patients), LS-associated (n=4, 3.0%), or LLS-associated (n=1, 0.8%) CRC.
Our data will be useful for genetic counseling in patients with synchronous CRCs suspected of having LS. Screening for LS using IHC for MMR proteins in individuals with multiple synchronous CRCs is an effective approach.
错配修复（MMR）缺陷（dMMR）的结直肠癌（CRC）主要分为三种亚型：甲基化型、林奇综合征（LS）相关型和林奇样综合征（LLS）相关型。尚无研究详细探讨同步诊断的dMMR CRC的患病率及亚型。因此，本研究旨在检查多个同步性CRC中dMMR状态的频率和分子特征，以阐明识别此类肿瘤患者的临床意义。
对2014年7月至2020年6月期间最初诊断为多个同步性CRC的连续患者经手术和内镜切除（结合手术切除）的病变进行MMR蛋白（MLH1、MSH2、MSH6和PMS2）的免疫组织化学（IHC）检测。必要时，进行甲基化分析以及种系和体细胞MMR基因检测。
共有133例患者（33例女性）有309个病变。同步肿瘤部位的组合为仅左侧结肠/直肠（n = 67，50.4%）、右侧结肠和左侧结肠/直肠均有（n = 42，31.6%）以及仅右侧结肠（n = 24，18.0%）。免疫组化显示，133例患者中有10例（7.5%）、309个病变中有17个（5.5%）至少一种MMR蛋白表达缺失。分子分析显示，这10例患者被分类为甲基化型（n = 5，占所有患者的3.8%）、LS相关型（n = 4，3.0%）或LLS相关型（n = 1，0.8%）CRC。
我们的数据将有助于对疑似患有LS的同步性CRC患者进行遗传咨询。对多个同步性CRC患者使用MMR蛋白免疫组化筛查LS是一种有效的方法。
