Study On Expression Of Mismatch Repair Genes HMLH1, HMSH2 And Cyclooxygenase -2 In Sporadic Colorectal Cancer

Objective:To study the expression of hMLH1, hMSH2 and COX-2 in sporadic colorectal cancer and explore their relevance with bionomics of sporadic colorectal cancer.Methods:The expression of hMLH1, hMSH2 and COX-2 were detected by immunohistochemical method (PV-9000 two-step method) in 52 cases of colorectal cancer,22 cases of colorectal adenoma and 20 cases of normal mucosa.The sum scores were calculated that were based on the dying depth and the number of positive cells.The score between 0 to 2 points was graded into negative and 3 points or more into positive. The data were analyzed using Chi-square test.The association were analyzed among expression of hMLH1,hMSH2,COX-2 and the bionomics of sporadic colorectal cancer.Pearson correlation analysis was used to analyze relationship between expression of hMLH1 and hMSH2 and expression of COX-2 in sporadic colorectal cancer.Results:1.The positive staining of hMLH1 protein were mainly located in the nucleus.The positive expression rates in normal mucosa, colorectal adenoma and sporadic colorectal carcinoma were 100.00%,77.27% and 75.00%.The lowest expression of hMLHl were found in sporadic colorectal cancer. There was significant difference in expression of hMLH1 between sporadic colorectal cancer and normal mucosa as well as between colorectal adenomas and normal mucosa(P<0.05).There was no significant difference between sporadic colorectal cancer and colorectal adenomas.The positive staining of hMSH2 was located in the nucleus.The positive expression of HMSH2 reduced in sporadic colorectal cancer.The positive expressive rates in normal mucosa,colorectal adenoma and sporadic colorectal carcinoma were 100.00%,82.82% and 78.85%.The expressive rates were gradually decreased.There was significant difference between sporadic colorectal cancer and normal mucosa(P<0.05).So did between colorectal adenomas and normal mucosa.There were no significant differences between sporadic colorectal cancer and colorectal adenomas.2.The expression of hMLHl and hMSH2 in sporadic colorectal cancer: Expression of hMLHl and hMSH2 had no correlation to patient's sex,age, tumor size,tumor site,lymph node metastasis and Dukes stages.The expression of hMLH1 and hMSH2 were associated with tumor histological differentiation.The positive expression rate of hMLH1,hMSH2 in poorly differentiated cancer groups by55.56% and 61.11%,respectively,were lower than that in the high and moderate differentiated cancer groups by 85.29% and 88.24%.The differences were significant by statistically analysis.3.The positive staining of COX-2 mainly located in the cytoplasm. Expression of COX-2 was gradually increased in normal mucosa, colorectal adenoma and sporadic colorectal carcinoma.The expression rate of COX-2 was 78.85% in sporadic colorectal cancer group,which was significantly higher than the expression rate of 54.55% in the colorectal adenomas and the expression rate of 5.00% in the normal mucosa group.There were statistically significant differences among the three groups (P<0.05).4.Expression of COX-2 were correlated with lymph node metastasis and Dukes stages,but had no correlation with gender,age,tumor size,tumor location and tumor histological differentiation in sporadic colorectal carcinoma.The expression rate of COX-2 was 89.28% in sporadic colorectal carcinoma with lymph node metastasis and 66.67% without lymph node metastasis.Significant difference was observed by statistically analysis.The expression rate of COX-2 was 92.86% in the groups of Dukes C and D stages,which was higher than that in the groups Dukes A and B stages by 62.50%.The difference was significant by the analysis.5.Correlation between expression of hMLH1 and hMSH2 and COX-2 in sporadic colorectal cancer:There were 36 cases with positive expression of hMLH1 and 5 cases with negative expression of hMLHl in 41 cases with positive expression of COX-2;There were 3 cases with positive expression of hMLH1 and 8 cases with the negative expression of hMLH1 in 11 cases with negative expression of COX-2;The correlation analysis,r=-0.571,P<0.01.There were 37 cases with positive expression of hMSH2 and 4 cases with negative expression of hMLHl in 41 cases with positive expression of COX-2;There were 4 cases with positive expression of hMSH2 and 7 cases with negative expression of hMLH1 in 11 cases with negative expression of COX-2;The correlation analysis,r=-0.539,P <0.01.Therefore,expression of hMLH1 and hMSH2 were negatively correlated to expression of COX-2 in sporadic colorectal cancer.Conclusion:1.Decreased expression of hMLH1 and hMSH2 were involved in the occurrence and development of colorectal cancer.Decreased expression of hMLH1, hMSH2 may be associated with degree of malignant in sporadic colorectal cancer.2.High expression of COX-2 may play an important role in the formation of colorectal cancer.The expression of COX-2 was correlated to lymph node metastasis and Dukes stages in sporadic colorectal carcinoma.3.Expression of hMLH1 and hMSH2 were negatively correlated to expression of COX-2 in sporadic colorectal cancer.