Correlation of p53 protein expression with apoptotic incidence in colorectal neoplasia

The wild-type p53 gene suppresses cell proliferation and induces apoptosis when it is transfected into human colon cancer cell lines. Therefore, mutation of the p53 gene, which correlates closely with p53 protein overexpression, would be predicted to activate cell proliferation and limit apoptosis. We tested this hypothesis by correlating p53 protein expression with cell proliferation and apoptosis in 70 neoplasms (29 adenomas and 41 carcinomas) using p53 and Ki-67 immunohistochemical staining and DNA nick end labelling. The p53 immunoreactivity was independent of the Ki-67 positivity. The apoptotic incidence was less frequent (P < 0.005) in tumours with diffuse p53 protein overexpression than in those with the sporadic overexpression, defined as p53 staining of isolated or scattered expression. In addition, apoptotic incidence only correlated directly (P < 0.05) with Ki-67 positivity in tumours with sporadic p53-protein expression. These results indicate that p53 protein that is expressed sporadically in colorectal neoplasms is probably wild-type protein and induces apoptosis in response to active cell proliferation. In contrast, diffusely overexpressed p53 protein in colorectal neoplasms is probably mutant and correlates with a reduction in apoptotic cell death independently of cell proliferation.