P53 AND P21(WAF1 CIP1/SDI1) GENE-PRODUCTS IN BARRETT-ESOPHAGUS AND ADENOCARCINOMA OF THE ESOPHAGUS AND ESOPHAGOGASTRIC JUNCTION/

The WAF1(CIP1/SDI1) gene encodes a cyclin-dependent kinase inhibitor w hich is induced by wild-type, but not mutated, p53 gene product. WAF1 immunohistochemistry has been suggested to clarify the phenotype of ov erexpressed p53 gene product. We evaluated both p53 and WAF1 gene prod ucts by immunohistochemistry in 98 esophagectomy specimens with Barret t esophagus and/or adenocarcinoma of the esophagus and esophagogastric junction. Diffuse positive p53 staining was found in 40 of 88 adenoca rcinomas (45%) and in dysplastic Barrett epithelium in 20 of 65 cases (31%), but not in Barrett mucosa without dysplasia (n = 36, P = .0004) . Eighty-eight percent of cancers exhibited WAF1 expression, but there was no association with p53 and WAF1 staining. WAF1 protein was also identified in Barrett epithelium and in esophageal squamous and gastri c epithelium. In contrast to carcinomas, a unique pattern of mutually exclusive p53 and WAF1 expression was found in five cases of dysplasti c Barrett epithelium; a missense mutation at codon 175 of p53 was iden tified in one. p53 staining of adenocarcinoma was associated with shor ter patient survival but was not independent of stage; WAF1 status add ed no prognostic information. Our findings show that WAF1 immunohistoc hemistry complements p53 immunohistochemistry in some cases of Barrett dysplasia but not in adenocarcinomas. Positive p53 immunostaining can serve to confirm a neoplastic process in Barrett mucosa. Positive sta ining of adenocarcinomas may be an indication of advanced stage. Copyr ight (C) 1996 by W.B. Saunders Company