IMMUNOHISTOCHEMICAL ANALYSIS OF P53 OVEREXPRESSION IN HUMAN COLONIC TUMORS

The progression from benign adenoma to colorectal cancer is underscore d by an accumulation of genetic defects involving the activation of pr otooncogenes and the inactivation by point mutations and deletions of tumor-suppressor genes. Altered p53 has been one of the most commonly observed of these defects. By using a monoclonal antibody, PAb1801, it was possible to detect the accumulation of an altered p53 protein in standard sections of colon-preserving histopathological criteria. We a nalyzed biopsies from benign and malignant colorectal tumors fixed in 70% ethanol, and detected cells positive for p53 in 65% of 34 carcinom as and 24% of 84 adenomas, but none in the normal-appearing adjacent m ucosa. No correlation was found between degree of differentiation of a denocarcinomas and p53 immunodetection. Abnormal p53 protein expressio n in adenomas ranged from sparsely stained to focally intensive areas. Overexpression of p53 was detected in more tumors taken from the left side of the colon than from the fight side. Adenomas with greater vil lous content and severe dysplasia had a greater tendency to overexpres s mutated p53. Cases of multiple synchronous adenomas showed different patterns of p53 expression but more positivity was found in adenomas from patients with a synchronous adenocarcinoma. Immunodetection of p5 3 in 11 biopsies from the same tumors alternatively fixed in 70% ethan ol or formalin gave comparable results for adenocarcinomas but was not consistent for adenomas. Fifty-four archival formalin-fixed paraffin- embedded colorectal tumors were also stained with PAb1801. p53 was det ectable, sometimes with a weaker intensity, in 50% of 18 adenocarcinom as and 22% of 36 adenomas, and most of these showed severe dysplasia. These results show that immunodetection of p53 overexpression could si gnificantly complement the histopathological diagnosis in predicting t he malignant potential of adenomas.