The Expression And Significance Of DNA Repair Gene Proteins In Carcinogenesis Of Colorectal Carcinoma

Objective: Colorectal carcinoma is a disease of threatenning our life and health severely. DNA repair genes can repair or cut many different kinds of gene damage for inhibiting transformation of wrong messages to offspring cells and preventing malignant transformation of cells. Mismatch repair (MMR) gene protein hMSH2 can repair mismatched bases in process of DNA replication and maintain genomic stability. The function of O6-methylguanine-DNA-methyltransferase (MGMT) is to protect DNA from aldyl agent damage and promoter from methylation. The products of homologous recombination repair gene-XRCC1 play an important role in repairing single-strand break and cutting wrong bases. Proto-oncogene activation and/or suppressor gene deactivation can induce normal cell to malignantly transform and develop. However, in the process, how DNA repair proteins express and whether they effect the expressions of proto-oncogene and suppressor gene are not clear. This study was designed to answer the questions by respectively detecting the expressions of DNA repair gene proteins in colorectal carcinoma, adjacent mucosa to carcinoma and normal tissue, and analyzing the relationships of their expressions to investigate the significance of DNA repair gene proteins expressions in colorectal carcinogenesis.Methods: Colorectal carcinoma tissues with pathological diagnosis of 68 patients and 30 adjacent tissues of these carcinoma patients were collected, 36 normal colorectal tissues were gotten. Immunohistochemistry was used to detect the protein expressions of hMSH2, MGMT, XRCC1, c-erbB-2 and P53 in all samples. SPSS13.0 statistic software was used to analyze the dates. Results: In carcinoma, adjacent and normal groups, the positive rates of hMSH2 expression were 83.82%(57/68), 80.0%(24/30) and 22.22%(8/36) respectively, which in the former two groups were significantly higher than that in the latter one(P<0.01); the positive rates of MGMT expression were 80.88%(55/68), 76.67%(23/30) and 8.33%(3/36) respectively, which in the former two groups were significantly higher than that in the latter one(P<0.01); the positive rates of XRCC1 expression were 94.12%(64/68), 96.67%(29/30) and 27.78%(10/36) respectively, which in the former two groups were significantly higher than that in the latter one(P<0.01). The positive rates of c-erbB-2 and P53 expression were 60.29%(41/68)and 50.0%(34/ 34)in carcinoma group respectively.In carcinoma group, the positive rate of MGMT expression in well-moderate differentiation group being 85.25%(52/61) was significantly higher than that in poor differentiation group being 42.86%(3/7)(P<0.01); but the expressions of hMSH2, MGMT, XRCC1 had no relationships with sex, age, location, differentiation, infiltrating depth, lymph node metastasis and Dukes staging (P>0.05) respectively.In carcinoma group, the expressions of c-erbB-2 and P53 had no relationships with sex, age, location, differentiation, infiltrating depth (P>0.05) respectively; but the positive rate of c-erbB-2 expression in group with lymph node metastasis being 82.86%(29/35) was significantly higher than that without lymph node metastasis being 36.36%(12/33)(P<0.05); the positive rate of c-erbB-2 expression in carcinoma of Dukes′C and D group being 82.86%(29/35) was significantly higher than that of Dukes′A and B group being 36.36%(12/33)(P<0.05); the positive rate of P53 expression in group with lymph node metastasis being 62.86%(22/35) was significantly higher than that without lymph node metastasis being 36.36%(12/33) (P<0.05); the positive rate of P53 expression in carcinoma of Dukes′C and D group being 62.86%(22/35) was significantly higher than that of Dukes′A and B group being 36.36%(12/33)(P<0.05).The expression of hMSH2 was correlated to the expression of MGMT in carcinoma group; but the clear correlations of DNA repair gene to c-erbB-2 and P53 expressions were not found in carcinoma group. Conclusions: 1. The expressions of hMSH2, MGMT and XRCC1 proteins were up-regulated in colorectal carcinoma tissues; and the expressions of hMSH2, MGMT and XRCC1 proteins were up-regulated in adjacent tissues.2. The expression of MGMT protein had direct correlation to the differentiation.3. The expressions of c-erbB-2 and P53 had direct correlation to lymph node metastasis and advance of tumor.4. It may be helpful to detect the expressions of hMSH2, MGMT and XRCC1 for predicating the happen of colorectal carcinoma.5. The expression of hMSH2 may effect on the expression of MGMT in colorectal carcinoma tissues.