CORRELATION OF P53 MUTATIONS WITH EPIDERMAL GROWTH-FACTOR RECEPTOR OVEREXPRESSION AND ABSENCE OF MDM2 AMPLIFICATION IN HUMAN ESOPHAGEAL CARCINOMAS

Esophageal carcinomas from 24 patients, most of whom were smokers and consumed alcoholic beverages daily, were analyzed for mutations in exo ns 5-8 of the p53 tumor suppressor gene. Mutations were identified by polymerase chain reaction amplification and direct sequencing in 12 of 24 (50%) of the samples; almost half of the mutations were at A:T bas e pairs. Nuclear accumulation of p53 protein, determined by immunohist ochemistry with the CM-1 polyclonal antibody, was observed in all case s in which a missense mutation in the p53 gene was detected. None of t he 24 carcinomas had amplification of the mdm2 gene, an alternate path way to p53 loss of function. Alterations involving three other cancer- related genes associated with human esophageal carcinogenesis, c-erbB- 1/epidermal growth factor receptor (EGFR), c-myc, and retinoblastoma ( Rb), were examined by Southern blot or immunohistochemical analysis in the same sample set to explore the possibility of a link between onco gene activation and loss of tumor suppressor function. While no associ ations were observed between amplification of the c-myc or EGFR genes and p53 abnormalities, a significant correlation (P < 0.01) was seen b etween the presence of p53 mutation and EGFR overexpression. Absence o f Rb protein, measured immunohistochemically, was observed in four tum ors, none of which had aberrations of the p53 gene. (C) 1993 Wiley-Lis s, Inc.