摘要/Abstract
摘要： 目的 ·探讨 DNA错配修复（ mismatch repair，MMR）系统蛋白 MLH1（mutL homolog 1）、MSH2（mutS homolog 2）、MSH6（mutS homolog 6）和 PMS2（postmeiotic segregation increased 2）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 > 6 cm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（ P0.012），KRAS基因突变患者的 MLH1缺失率显著低于未突变患者（ P0.044）。这些 SCRC患者中， MLH1和 PMS2蛋白阳性表达率差异无统计学意义（ P1.000）。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。
关键词: 散发性结直肠癌, 错配修复, MLH1, 免疫组织化学
Abstract:
Objective · To investigate the s 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 April 2014 to August 2018 were collected. MLH1, MSH2, MSH6, PMS2 and p53 proteins in colorectal cancer tissue samples 209 patients who met the criteria were detectedimmunohistochemistry, and 67 samples were detectedreal-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 (P0.012); MLH1 deficiency rate of the patients with KRAS mutation was significantly lower than that of unmutant patients (P0.044). There was no significant difference in the positive rates of MLH1 and PMS2 in these SCRC patients (P1.000). 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.
Key words: sporadic colorectal carcinoma, mismatch repair (MMR), mutL homolog 1 (MLH1), immunohistochemistry
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