| Objectives: Mismatch repair gene is a group of highly conservative home keeper gene, its main function is to repair errors caused by wrong base pairs,base insertion,deletion and other injuries which occur during the bases replication and reorganization, so it is an important role to keep DNA faithful replication and genome stability. The mutation of mismatch repair gene is closely related with hereditary non-polyposis colorectal cancer(HNPCC), but its mutation mechanism in sporadic colorectal cancer remains unclear, besides, there is current controversy of the relationship between mismatch repair gene mutation and chromosomal instability which is caused by oncogene or tumor suppressor gene mutation. In this study, immunohistochemistry was used to detect the protein expressions of hMLH1,hMSH2 and P53 to analyze the dissemination of abnormal mismatch repair genes protein expression in sporadic colorectal cancer its relationship with chromosome instability.Methods: clear diagnosed colorectal cancer 165 cases, adenoma polyps 32 cases, normal mucosa 37 cases were collected, and use immunohistochemical method to detect the hMLH1,hMSH2 and P53 protein expression in colorectal cancer and colorectal cancer, and analys the relationship between hMLH1,hMSH2 and P53 protein expression in sporadic colorectal cancer, while analys the relationship of these three gene protein expression with gender,age,tumor location,differentiation,invasion depth, metastasis and other clinical features.Results:1. The expression of hMLH1 and hMSH2The positive expression rates of hMLH1 and hMSH2 in normal mucosa , colorectal adenoma ,sporadic colorectal cancer group were 100%,84.4% ,81.2% and 100% ,87.5% ,87.3% ,which were gradually decreasing. There was significant difference between colorectal cancer and colorectal adenoma group with normal mucosa group (P<0.05), but no significant difference between the colorectal cancer group and adenoma group (P> 0.05).2. The relationship between hMLH1,hMSH2 protein expression and different clinical characteristics(1) In sporadic colorectal cancer , the positive expression rates of hMLH1 and hMSH2 in young group(≤50 years),middle group (51-69 years) ,elder group (≥70 years) were 68.8% ,82.4% ,87.5% and 75.0%,85.9%,97.9%. The expression of hMLH1 and hMSH2 in young group were significant lower than elder group (P<0.05). The positive rate of hMLH1 in male patients was 78.1% ,which was significant lower than female patients of 85.5% (P <0.05); the positive rate of hMSH2 in these two groups were 85.4% and 89.9%, the rate of male patients was also slightly lower than women patients, but there was no significant difference (P> 0.05). The expressions of hMLH1 and hMSH2 had no relationship with the tumor location,invasived depth,lymph node metastasis and Ducks stage (P>0.05).In well-moderate differentiated carcinoma ,poor differentiated carcinoma and mucinous carcinoma,the positive rates of hMLH1 and hMSH2 were 84.5% ,64.7% ,50% and 90.8% ,70.6% ,50% , which were gradually decreasing, and the positive rate in well-moderate differentiated carcinoma was significant higher than poor differentiated carcinoma and mucinous carcinoma (P<0.05),but there was no significant difference between poor differentiated carcinoma and mucinous carcinoma (P>0.05).(2) In colorectal adenoma, the positive expression rates of hMLH1 and hMSH2 in young group(≤50 years),middle group (51-69 years)and elder group (≥70 years)were 66.7%,83.3%,92.9% and 50.0%,91.7%,100%,which were significant lower in young group than elder group (P<0.05).The positive expression rate of hMLH1 in low-moderate grade dysplasia was 88.9%,which was higher than the 60% rate of high grade dysplasia,but no significant difference (P>0.05), the positive expression rate of hMSH2 in these two groups were 92.6% and 60%,which had no significant difference (P>0.05). The positive expression of hMLH1 and hMSH2 had no relationship with the patiens′gender and tumor location (P>0.05).3. The expression of p53 and its relationship of different clinical characteristics(1) The positive expression rate of p53 in normal mucosa,adenoma, sporadic colorectal cancer group was 0%,21.9% and 48.5%, which was gradually creasing, and with significant difference between each group (P<0.05) .(2) In sporadic colorectal cancer , the positive expression rate of p53 in well-moderate differentiated carcinoma ,poor differentiated carcinoma and mucinous carcinoma was 53.5%,17.6% and 16.7%,which was significant higher in well-moderate differentiated carcinoma than poor differentiated carcinoma and mucinous carcinoma (P<0.05),but there was no significant difference between poor differentiated carcinoma and mucinous carcinoma (P>0.05); the positive expression rate of p53 in serosa un-infiltrated tumor and infiltrated tumor was 72.7% and 36.4%,which was significant higher in the first group (P<0.05). The expressions of p53 had no relationship with the patiens′gender,age,tumor location,lymph node metastasis and Ducks stage (P>0.05).(3) In colorectal adenoma, the positive expression rate of p53 in low-moderate grade dysplasia and high grade dysplasia was 18.5% and 40%,which was higher in the high grade dysplasia than the low-moderate grade dysplasia, but no significant difference (P>0.05).4. The collection between hMLH1, hMSH2 and p53 protein expressionThere were no significant correlation between the hMLH1,hMSH2 protein expression and p53 protein expression both in sporadic colorectal cancer group and colorectal adenoma group (P>0.05).Conclusions:1. The protein expression of hMLH1 and hMSH2 were lower in sporadic colorectal cancer, which means there may be some relationship between this two mismatch repair genes and sporadic colorectal cancer's occurrence. 2. In sporadic colorectal cancer, the lost expression of hMLH1 and hMSH2 was more frequently in young and male patients, which means the tumor with mismatch repair gene mutation had special clinical features.3. hMLH1 and hMSH2 protein expression became lower companying the decrease of tumor malignancy, and may be related to malignancy or benignity of tumor.4. There was a subset lost of hMLH1 and hMSH2 protein expression in colorectal carcinoma, and it was more frequently in high grade dysplasia, which means the two mismatch repair genes had a subset mutation rate in carcinoma and may proved the occurrence of colorectal cancer.5. The protein expression of p53 was gradually creasing in colorectal carcinoma and colorectal cancer group, which means the mutation of p53 may be related to the occurrence of colorectal cancer.6. There was no significant correlation between the hMLH1,hMSH2 protein expression and p53 protein expression in both sporadic colorectal cancer group and colorectal adenoma group, which means the mismatch repair gene mutation and tumor suppressor gene mutation may be two different ways to conduce tumors.
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