The Significance Of MGMT,p53 Protein Expression In Sporadic Colorectal Cancer

Background and objective:DNA repair gene is an important role to keep DNA faithful replication and genome stability, and DNA repair failure is known to be a critical part for many types of cancers. Among that, The DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is an enzyme that repairs O6-methylguanine, base damaged by endogenous and environmental alkylating agents. Comparing the mass foreign reports, there are a few reports in China about the correlation between the abnormal expression of MGMT and sporadic colorectal cancer. Especially, the knowledge about the gene expression in adenoma polyps is limited, which is very important to comprehend the progression of colorectal carcinogenesis. This study performed immunohistochemical staining to detect the ex- pression of DNA repair gene MGMT and tumor suppressor gene p53, and analyze the roles of their abnormal expressions in co1orecta1 carcinoma.Method: The samples of primary tumor tissues from sporadic colo- rectal carcinoma patients (n=86) during surgery in the three hospitals of Dalian .corresponding surgical margin tissues were collected from 31 colorectal carcinoma patients. In addition, we carried out 34 adenoma polyps. We performed immunohistochemical staining to detect the MGMT and p53 protein expression in colorectal adenoma and colorectal cancer. And also this study analysis the relationship between MGMT and p53 protein expression in sporadic colorectal cancer, while analysis the relation- ship of these two genes protein expression with the clinical features of gender, age, tumor location, differentiation, invasion depth and metastasis. Statistical analyses were conducted using SPSS 15.0 software. Result:1. The expression of MGMTThe positive expression rate of MGMT in sporadic colorectal cancer group, colorectal adenoma group, surgical margin group was 87.10% (27/31),64.70%(22/34),40.69%(35/86) ,The positive rate of MGMT protein expression was significantly reduced in sporadic colorectal cancer group compared with the other groups, .The positive expression rate of MGMT in colorectal adenoma group was lower than that in the surgical margin group. There was significant difference among these three groups (X2=6.44,X2=5.88,X2=4.38,p<0.05).2. The relationship between MGMT protein expression and different clinical characteristics(1).In sporadic colorectal cancer, the expressions of MGMT had no relationship with the gender, age, tumor location, differentiation, invasion depth and metastasis (P>0.05).(2).In colorectal adenoma, the positive expression rates of MGMT. in low-moderate grade dysplasia group was77.3%, which was higher than the rate of 41.7% in high grade dysplasia group, there was significant difference between these two group(P<0.05).But the positive expression of MGMT had no relationship with the patients'gender ,age ,tumor location (P>0.05).3. The expression of p53 protein and the relationship between its expression and different clinical characteristics.(1) The positive expression rate of p53 in colorectal cancer, adenoma surgical margin group was 6.67%(2/30), 26.47%(9/34) and 48.84%(42/86), The positive rate of p53 protein expression was significantly increased in sporadic colorectal cancer group compared with the other groups, The positive expression rate of MGMT in colorectal adenoma group was higher than that in the surgical margin group. There was significant difference among these three groups (P<0.05).(2)In sporadic colorectal cancer, the positive expression rate of p53 in the group of well differentiated carcinoma, moderate carcinoma and poor differentiated carcinoma the was 35.4 %,61.5 % and 90 % .There was significant difference among these three group(P<0.05).But, the expressions of p53 had no relationship with the patients'gender, age ,tumor location, and lymph node metastasis (P>0.05).(3)In colorectal adenoma, the positive expression rate of p53 in the low-moderate grade dysplasia group and high grade dysplasia group was 22.7%and33.3%, there was significant difference between these two group(P<0.05).4. The correlation between MGMT and p53 protein expression(1).There were negative correlation between the expression of MGMT and p53 protein in sporadic colorectal cancer group (R=-2.41, P<0.05).(2). There were no significant correlation between the MGMT protein expression and p53 protein expression in the colorectal adenoma group (P>0.05).Conclusion:1. The expression of MGMT protein was down-regulated in sporadic colorectal cancer, which may relate to the occurrence of colorectal cancer.2. There was down-regulation of MGMT protein expression in colo- rectal carcinoma, and it was more frequently in high grade dysplasia, which means the down regulation of MGMT expression may happened in the early stage of colorectal adenoma, which may promote the progression of colo- rectal adenoma.3. The expression of p53 protein was down-regulated in colorectal carcinoma, which may be related to the occurrence of sporadic colorectal cancer.4. There was p53 protein over expression in colorectal adenoma, and it was more frequently in high grade dysplasia, which means the over ex- pression of MGMT protein may happened in the early stage of colorectal adenoma, which may promote the progression of colorectal adenoma.5. There is negative correlation between the expression of MGMT and p53 protein in sporadic colorectal cancer. The down regulation of MGMT expression and over expression of p53 protein may involve in the occur- rence of sporadic colorectal cancer.6. Detecting the expressions of MGMTandp53 expression are very helpful to predict colorectal carcinoma.