Comparative evaluation of the expression of cell cycle regulating proteins: cyclin D1, P53 and P21 (WAF1) in colorectal cancer.

Cyclin D1, P53 and P21 (WAF1) are cell cycle regulating proteins, playing a crucial role in oncogenesis of a large number of human malignancies, and loss of activity of P53 and P21 (WAF1) proteins seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. To find out their mutual relations we investigated the expression of cyclin D1, P53 and P21 (WAF1) in 122 colorectal cancers by immunohistochemistry. Positivity for cyclin D1 was found in all the cases (100%), positivity for P53 in 96 cases (70%) and positivity for P21 in 48 cases (39%). Statistical analysis revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and also between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity. These data suggest that in colorectal cancer induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. Wild-type P53, which is undetectable by immunohistochemistry, induces transcriptionally P21 (WAF1) and in tumours it may cause its accumulation, while mutations of the P53 may result in a sufficient increase of intracellular protein having no ability to transactivate P21 (WAF1). Moreover P21 (WAF1) as the main cyclin-dependent kinases (CDKs) inhibitor may also inhibit the activity of the cyclins, thus overexpression of P21 (WAF1) may result in reduced level of cyclin D1.