Expression Differences Of MLH1 And MSH2 Proteins In Colon Cancer And Their Relationship With Clinicopathologic Characteristics

Objective:By using immunohistochemistry(IHC)and capillary electrophoresis(CE)which was used to detect microsatellite instability(MSI)to investigate the expression differences of mismatch repair(MMR)genes MLH1 and MSH2 and the MSI status in colon cancer.The relationship between MLH1 and MSH2 proteins expression and age,sex,tumor location,tumor differentiation degree,tumor pathological type and TNM stage was analyzed.The results of the two methods were analyzed to guide clinicians to make individualized treatment plans for colon cancer.It has important clinical significance in screening,classification,diagnosis,treatment and prognosis of colon cancer.Methods: The pathological and clinical data of 220 patients who had undergo radical colon cancer surgery in the Fourth Affiliated Hospital of China Medical University from2015 to 2020 were collected.Immunohistochemistry was used to detect the expression of mismatch repair genes MLH1 and MSH2 proteins.The 220 patients were divided into two groups: d MMR group(negative protein expression group)(n = 57)and p MMR group(positive protein expression group)(n = 163),and the corresponding clinicopathological characteristics were analyzed and compared between these two groups.At the same time,subgroup analysis was performed on the d MMR group.According to the presence or absence of family genetic history,the d MMR group was divided into group A(20 cases with family genetic history)and group B(37 cases without family genetic history).MSI test was performed on the samples of group A and the results were compared with those of IHC to analyze the coincidence rate of the test results of the two methods.d MMR is equivalent to MSI-H and p MMR is equivalent to MSI-L or MSS.Results: Immunohistochemical results: Among the 220 patients,a total of 57 cases(25.91%)showed negative expression of mismatch repair proteins,including 49 cases(22.27%)of negative expression of MLH1 protein,17 cases(7.73%)of negative expression of MSH2 protein,and 9 cases(4.09%)of negative expression of both of them.Among the 57 patients in the d MMR group,34 patients(59.65%)whose tumors were located in the right colon,15 patients(26.32%)who had mucinous adenocarcinoma,39 patients(68.42%)who had high-middle differentiation,40 patients(70.18%)whose TNM stage is I or II,and 42 patients(73.68%)who had no lymph node metastasis.Among 163 patients in p MMR group,72 patients(44.17%)had tumors located in the right colon,11 patients(6.75%)had mucinous adenocarcinoma,87 patients(53.37%)had high-middle differentiation,81 patients(49.69%)had TNM stage is I or II and 87 patients(53.37%)had no lymph node metastasis.There were statistically significant differences in the clinicopathological aspects of tumor site,tumor differentiation type,tumor pathological type,TNM stage and lymph node metastasis between the two groups(P < 0.05),but there were no statistically significant differences in the gender and age of patients between the two groups(P > 0.05).MSI test results:After MSI test for group A(20 patients with family genetic history),17 patients(85.00%)were MSI-H,2 patients(10.0%)were MSI-L,and 1 patient(5.0%)was MSS.The coincidence rate between IHC and MSI was 85.00%.Conclusion: 1.The negative expression of MLH1 and MSH2 was dominated by MLH1 protein.The negative expression rate of MLH1 and MSH2 protein was 22.27% and7.73%,respectively;2.Colon cancer with negative expression of MLH1 and MSH2 proteins was more common in the right colon;3.Mucinous adenocarcinoma was the most common pathologic type of colon cancer with negative expression of MLH1 and MSH2 proteins.4.The TNM stage of colon cancer tumors with negative expression of MLH1 and MSH2 was earlier(mostly in stage I and II),and the lymph node metastasis of colon cancer with negative expression of MLH1 and MSH2 was less,suggesting that the prognosis of colon cancer patients with negative expression of MLH1 and MSH2 were better than that of patients with positive expression.6.The coincidence rate of these two methods was 85%.These two methods can be used as the primary screening method for d MMR /MSI-H,and can be used to evaluate the clinicopathological characteristics and prognosis of patients with colon cancer who have not undergone surgery.