Study On The Aberrant Of P16 Gene And Mismatch Repair Genes In Colorectal Cancer

Colorectal cancer (CRC), with its incidence keeping rising in the last two decades, has become the prevalent cancer in the world today, and it ranks the third as a cause of death from cancer overall. In China, this cancer ranks third in frequency of death. It is clearly important to understand the basis of carcinogenesis and tumorgenesis of this cancer, and to develop effective molecular diagnostic methods for early detection and therapeutic intervention in colorectal cancer.In the present study, using methylation specific-PCR and immunochemical method of SP, the hypermethylation of p16 promoter and expression of p16 gene were detected in tumor tissues from patients with colorectal cancer. The LOH(Loss of Heterozygosity) of hMLH1,hMSH2,hPMS1,hPMS2,hMSH3, hMSH6 and p16 gene also were analyzed in colorectal cancer. The results are as follows:① The frequency of p16 promoter methylation is 41% in patients with CRC, which shows the p16 promoter methylation is one of the common alteration in tumor tissues of CRC.② The frequency of p16 promoter methylation is higher in Dukes stages of C and D CRC (59%) than A and B CRC (20%)(p<0.05). In tumor cells from high and media polarization tumor (30%), the frequency of p16 promoter methylation is 30%, which is significant different from that in the low polarization tumor (100%). Hypermethylation of p16 was more frequently observed in CRC with lymph nodes metastasis than that in CRC without lymph nodes metastasis.③ The p16 protein can express highly in colorectal cancer tissue (75.7%). we found that early stage cancer of the Dukes stages A and B has the higher expression frequency (80%) than that in Dukes stages C and D stages CRC (71%), but with no statistical significance (p>0.05). In the high and media polarization cancer, the rate of expression of p16 protein is clearly higher than that in the low polarization cancer (87% vs 17%, p<0.01). The of p16 protein in lymph node metastasis CRC expressed highly than that in no metastasis CRC.④ The LOH frequence of p16 gene is 31.7% in CRC patients, which indicates LOH is one of the mechanism to inacvtivate p16 expression. The LOH frequences of hPMS2, hMSH, hMSH3 and hMLH12/ hMSH6 gene in⑤ CRC are 30%,25%,26.7%, and 26.3% respectively. No LOH of Hpms1 gene was found in CRC. The low expression of mismatch repair genes may be indused by loss of one allele of these genes.