Over-expression of p53 nuclear oncoprotein in colorectal adenomas

Abstract

p53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53 protein is undetectable by standard immunohistochemical staining and the over-expression found in neoplastic cells correlates with the presence of point mutations of evolutionary conserved regions of the p53 gene. We examined the expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17 tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19 moderate, 6 severe), 11 moderately differentiated adenocarcinomas (6 Duke's A, 4 Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1 which recognises p53 protein in conventionally fixed and processed histological material. We found that 15 out of 36 colorectal adenomas showed p53 immunoreactivity, although in 4 positive cases (26%) the staining was very focal (less than 0.1% positive cells). More than 80% of severely dysplastic adenomas showed strong p53 immunoreactivity and this over-expression was correlated with increased cell proliferative rate as detected by the proliferating-cell-nuclear-antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%) colorectal adenocarcinomas as previously shown. Our data suggest that the p53 gene mutation, with the subsequent over-expression of the protein, occurs in colorectal adenomas and may therefore be a fundamental genetic event underlying the dysplasia and loss of proliferative control that are characteristic of adenomas with malignant potential.