P53 overexpression in squamous cell carcinoma of the esophagus.

Abstract

Coastal South Carolina has a high incidence of squamous cell carcinoma of the esophagus (SCCE) among black residents. Overexpression and mutations of the p53 tumor suppressor gene have been noted in SCCE from other high-incidence regions. The purpose of this study was to determine the frequency of p53 overexpression in this region both in patients with SCCE and in normal subjects. Normal and malignant tissue obtained at esophagoscopy and normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal antibodies to the p53 gene product. Total cellular RNA was extracted from SCCE, reverse transcribed to complementary DNA, and a portion of the p53 gene was amplified via polymerase chain reaction and sequenced. Immunohistochemical studies on SCCE from nine patients showed that six (67%) were positive, two (22%) were negative, and one was indeterminate for p53 overexpression. The corresponding normal samples showed that three (33%) had p53-positive cells in the basal epithelial layer, whereas six did not. NEM from 18 random forensic cases displayed p53 overexpression in seven (39%). Eight of the nine tumors had p53 mutations. p53 overexpression and mutations are frequently found in SCCE from patients in coastal South Carolina. Overexpression in normal epithelium from random autopsy cases may indicate an inherited or acquired predisposition in this geographic region.