散发性结直肠癌DNA错配修复系统蛋白表达及其临床意义

Expression and clinical significance of DNA mismatch repair proteins in sporadic colorectal carcinoma

目的·探讨DNA错配修复(mismatch repair,MMR)系统蛋白MLH1(mutL homolog1)、MSH2(mutS homolog2)、MSH6(mutS homolog6)和PMS2(postmeiotic segregation increased2)在散发性结直肠癌(sporadic colorectal carcinoma,SCRC)中的表达及与临床病理特征之间的关系。方法·收集2014年4月-2018年8月在上海交通大学医学院附属同仁医院行结直肠癌根治术的SCRC患者的癌组织样本。采用免疫组织化学法检测符合标准的209例患者的结直肠癌组织样本中的MLH1、MSH2、MSH6、PMS2和p53蛋白,并对其中67例癌组织行荧光定量PCR检测KRAS癌基因突变情况。结果·209例患者的癌组织中,MLH1、MSH2、MSH6及PMS2蛋白缺失率分别为17.2%(36/209)、2.4%(5/209)、12.9%(27/209)、16.7%(35/209)。MMR系统蛋白总的缺失率为30.1%(63/209),在55岁以下、肿瘤位于右半结肠、肿瘤直径>6cm及黏液腺癌的SCRC患者中较高(均P<0.05)。p53基因突变患者的MLH1缺失率显著高于未突变患者(P=0.012),KRAS基因突变患者的MLH1缺失率显著低于未突变患者(P=0.044)。这些SCRC患者中,MLH1和PMS2蛋白阳性表达率差异无统计学意义(P=1.000)。结论·MMR系统蛋白缺失可能与SCRC患者年龄、肿瘤位置、肿瘤大小和病理组织分型相关,MLH1蛋白缺失可能与p53基因及KRAS基因的突变相关。

Objective · To investigate the expressions of mismatch repair (MMR) proteins, i.e. MLH1 (mutL homolog 1), MSH2 (mutS homolog 2), MSH6 (mutS homolog 6) and PMS2 (postmeiotic segregation increased 2) in sporadic colorectal carcinoma (SCRC) and their correlation with clinicopathological characteristics. Methods · Cancer tissue samples of the SCRC patients who underwent radical resection of colorectal cancer at Tongren Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to August 2018 were collected. MLH1, MSH2, MSH6, PMS2 and p53 proteins in colorectal cancer tissue samples from 209 patients who met the criteria were detected by immunohistochemistry, and 67 samples were detected by real-time PCR for KRAS oncogene mutation. Results · In 209 cases of cancer tissues, MLH1, MSH2, MSH6 and PMS2 deficiency rates were 17.2%(36/209), 2.4%(5/209), 12.9%(27/209), and 16.7%(35/209), respectively. The total deficiency rate of MMR system proteins was 30.1%(63/209), which was higher in the patients under 55 years old, with tumor at the right colon, with tumor bigger than 6 cm or with mucinous adenocarcinoma (all P<0.05). MLH1 deficiency rate of the patients with p53 mutation was significantly higher than that of unmutated patients (P=0.012);MLH1 deficiency rate of the patients with KRAS mutation was significantly lower than that of unmutant patients (P=0.044). There was no significant difference in the positive expression rates of MLH1 and PMS2 in these SCRC patients (P=1.000). Conclusion · MMR systemic protein deletion may be associated with patient age, tumor location, tumor size, and histopathological typing;MLH1 protein deletion may be associated with mutations of p53 and KRAS genes.