Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.
目的： 深入探讨散发性错配修复缺陷（dMMR）结直肠癌的临床病理学特征，并分析影响其预后的关键因素。 方法： 回顾性收集2015年7月至2021年4月在中国医学科学院 北京协和医学院 北京协和医院接受治疗的120例散发性dMMR结直肠癌患者的资料。根据家族史及二代测序检测结果排除林奇综合征患者，排除同时性多发结直肠癌术前进行放化疗等抗肿瘤治疗以及随访资料缺失的患者。采用免疫组织化学方法检测错配修复蛋白的表达情况，利用甲基化特异性PCR方法进行甲基化检测，通过荧光PCR方法对BRAF V600E基因突变进行筛查。主要观察指标包括临床病理资料、基因突变状况、随访数据以及生存与预后分析。预后指标主要关注疾病无进展生存期和总体生存期。 结果： 散发性dMMR结直肠癌更常见于右半结肠、女性和老年患者，形态学以中分化居多，存在低级别肿瘤出芽的患者占多数。免疫组织化学表达方面，以MLH1、PMS2缺失为主，且蛋白表达有年龄及部位的特殊性。MLH1甲基化多见于老年女性患者，而在MLH1和PMS2缺失的年轻男性患者中较为少见。BRAF V600E基因突变在右半结肠的肿瘤中检出频率更高（P<0.05）。此类肿瘤患者的3年和5年无进展生存率分别为90.7%和88.7%，3年和5年总体生存率分别为92.8%和90.7%。肿瘤出芽状态是影响肿瘤复发的独立危险因素（风险比=3.375，95%置信区间：1.060~10.741，P=0.039），其中低级别肿瘤出芽的患者预后较好，而中、高级别肿瘤出芽的患者预后较差。 结论： 在散发性dMMR结直肠癌患者中，肿瘤出芽状态是影响肿瘤复发的独立危险因素。.