Patients with pancreatic cancer (PC) showing mismatch repair (MMR) deficiency may benefit from immunotherapy. Microsatellite instability (MSI) is a hallmark of MMR deficiency (MMR-D). Here, we estimated the prevalence of MSI in PC, investigated germline and somatic mutations in the three MMR genes (MLH1,MSH2, andMSH6), and assessed the relationship between MMR genes mutations and MSI status in PC. Clinical specimens from PC patients were analyzed using targeted next-generation sequencing, including paired normal and tumor specimens from 155 patients, tumor-only specimens from 86 patients, and normal-only specimens from 379 patients. The MSI status of 235 PCs was assessed via PCR. Pathogenic/likely pathogenic (P/LP) germline variants in the MMR genes were identified in 1.1% of patients, while somatic variants were found in 2.6% of patients. No MSI-H tumors were detected. One patient carried two variants (P (VAF = 0.57) and LP (VAF = 0.25)) simultaneously; however, their germline/somatic status remains unknown due to the investigation focusing solely on the tumor and MSI analysis was not performed for this patient. MSI is rare in PC, even in tumors with MMR genes mutations. Our findings underscore the importance of assessing tumor MMR-D status in PC patients with confirmed Lynch syndrome when deciding whether to prescribe immunotherapy.
胰腺癌（PC）患者若存在错配修复（MMR）缺陷可能从免疫治疗中获益。微卫星不稳定性（MSI）是MMR缺陷（MMR-D）的标志性特征。本研究旨在评估PC中MSI的发生率，探究三种MMR基因（MLH1、MSH2和MSH6）的胚系与体细胞突变情况，并分析PC中MMR基因突变与MSI状态之间的关联。通过靶向二代测序技术对PC患者的临床样本进行分析，包括155例患者的配对正常与肿瘤样本、86例患者的仅肿瘤样本以及379例患者的仅正常样本。采用PCR技术对235例PC样本的MSI状态进行评估。结果显示，1.1%的患者携带MMR基因的致病性/可能致病性（P/LP）胚系变异，2.6%的患者存在体细胞变异。所有肿瘤中均未检测到MSI-H状态。一例患者同时携带两种变异（P型（VAF=0.57）和LP型（VAF=0.25）），但由于该病例仅进行了肿瘤样本检测且未行MSI分析，其胚系/体细胞状态尚未明确。研究表明，MSI在PC中较为罕见，即使在存在MMR基因突变的肿瘤中亦然。本发现强调，对于确诊林奇综合征的PC患者，在决定是否采用免疫治疗时，评估肿瘤MMR-D状态具有重要意义。
Mutations in Mismatch Repair Genes and Microsatellite Instability Status in Pancreatic Cancer
肿瘤(癌症)患者之家