Published in Cancer Detection and Prevention 1994; 18(3):187-196.

Immunohistochemical Analysis of p53 Overexpression in Human Colonic Tumors

Elisabeth Darmon, MS, Karen R Cleary, MD1, Michael J Wargovich, PhD

Dept of Gastrointestinal Oncology and Digestive Diseases, Dept of Pathology1, The Univ of Texas M.D. Anderson Cancer Center, Houston, Texas

Address all correspondence and reprint requests to: Elisabeth Darmon, U.T.M.D. Anderson Cancer Center, Dept of Gastrointestinal Medical Oncology and Digestive Diseases, Box 78, 1515 Holcombe Blvd, Houston, Texas 77030

ABSTRACT: The progression from benign adenoma to colorectal cancer is underscored by an accumulation of genetic defects involving the activation of protooncogenes 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, PAb 1 80 1, it was possible to detect the accumulation of an altered p53 protein in standard sections of colon-preserving histopathological criteria. We analyzed biopsies from benign and malignant colorectal tumors fixed in 70% ethanol, and detected cells positive for p53 in 65% of 34 carcinomas and 24% of 84 adenomas, but none in the normal- appearing adjacent mucosa. No correlation was found between degree of differentiation of adenocarcinomas and p53 immunodetection. Abnormal p53 protein expression 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 right side. Adenomas with greater villous content and severe dysplasia had a greater tendency to overexpress 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 p53 in 11 biopsies from the same tumors alternatively fixed in 70% ethanol 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 PAbl80l. p53 was detectable, sometimes with a weaker intensity, in 50% of 18 adenocarcinomas and 22% of 36 adenomas, and most of these showed severe dysplasia. These results show that immunodetection of p53 overexpression could significantly complement the histopathological diagnosis in predicting the malignant potential of adenomas.

KEY WORDS: p53, colorectal adenomas, adenocarcinomas, immunohistochemistry.