Expression and clinical significance of DNA mismatch repair proteins in sporadic colorectal carcinoma / 上海交通大学学报（医学版）

ABSTRACT

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.