Relationship Between The Cell Cycle Regulation Factors Expression And Prognosis In Colorectal Carcinoma

Objective To analyze the correlation of cell cycle regulation factors Cyclin D1, CDK.4, P1 6 protein and p16 gene expression with clinicopathologic features and the prognosis in colorectal carcinoma.Methods Cyclin D1, CDK4 and P16 protein expression were examined with SP immunohistochemical technique in 89 cases of colorectal carcinoma and 12 cases of normal colorectal tissues, all patients were followed-up after operation. p16 gene was detected with SSCP-PCR technique in 40 cases of colorectal carcinoma. The relationships were analyzed among the Cyclin D1, CDK4, P16 protein and p16 gene expression with clinical staging, pathological grading, lymph node metastases and survival rates of patients with colorectal carcinoma.Results The positive staining of Cyclin Dl was located in nucleus, P16 and CDK4 were located in cytoplasm and nucleus in colorectal carcinoma. The positive staining was only located in cytoplasm for P16 and CDK4 and no positive staining for Cyclin Dl in normal colorectal tissues. In colerectal carcinomas, the expression rate of Cyclin Dl was 42.69% (38/89) in nucleus, P16 was 57.30% (51/89) in cytoplasm and 47.19% (42/89) in nucleus, CDK4 was 92.13% (82/89) in cytoplasm and 22.72 % (22/89) in nucleus. The expression rate of P16 and CDK4 were 25.00% (3/12) and 41.66% (5/12) respectively in normal colorectal tissues and lower than those of colorectal carcinoma (P<0.05) significantly. The expression of Cyclin Dl was found to have a significant association with lymph node metastasis and survival rates (P0.05), but not related remarkably to clinical staging, pathological grading (P>0.05). The expression of CDK4 in nucleus was correlated with pathological grading (P<0.05), but not related to clinical staging, lymph node metastases and survival rates (P>0.05). The expressions of both CDK4 and P16 in cytoplasm and that of P16 in nucleus were not shown significant association with clinical stage, pathological grade, lymph node metastases and survival rates. Furthmore, The expressions of both Cyclin D1 and P16 had significant positiveassociations with CDK4 expression in nucleus (P<0.05). In addition, p16 gene deletion rate was 47.50% (19/40) and it had close relation with histological classification (P<0.05). There was a positive correlation in the expression of p16 gene and P16 protein (P<0.05).Conclusions The positive expression of Cyclin D1, that is a indication of the poor prognosis, is closely related with lymph node metastasis of colorectal carcinoma. Particularly, to cases in stage Dukes' B , the above evaluation is much more significant. To some extent, the p16 gene detection and CDK4 positive expression in nuclear are closely associated with cell differentiation. The abnormal regulation of Cyclin Dl / CDK4 / P16 factors may be one of the causes of colorectal carcinoma.