CORRELATION OF P53 PROTEIN EXPRESSION WITH APOPTOTIC INCIDENCE IN COLORECTAL NEOPLASIA

The wild-type p53 gene suppresses cell proliferation and induces apopt osis when it is transfected into human colon cancer cell lines. Theref ore, mutation of the p53 gene, which correlates closely with p53 prote in overexpression, would be predicted to activate cell proliferation a nd limit apoptosis. We tested this hypothesis by correlating p53 prote in expression with cell proliferation and apoptosis in 70 neoplasms (2 9 adenomas and 41 carcinomas) using p53 and Ki-67 immunohistochemical staining and DNA nick end labelling. The p53 immunoreactivity was inde pendent of the Ki-67 positivity. The apoptotic incidence was less freq uent (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 on ly correlated directly (P<0.05) with Ki-67 positivity in tumours with sporadic p53-protein expression. These results indicate that p53 prote in that is expressed sporadically in colorectal neoplasms is probably wild-type protein and induces apoptosis in response to active cell pro liferation. In contrast, diffusely overexpressed p53 protein in colore ctal neoplasms is probably mutant and correlates with a reduction in a poptotic cell death independently of cell proliferation.