ASSOCIATION OF TRANSFORMING GROWTH-FACTOR-ALPHA (TGFA) AND ITS PRECURSORS WITH MALIGNANT CHANGE IN BARRETTS EPITHELIUM - BIOLOGICAL AND CLINICAL-VARIABLES

Adenocarcinomas of the gastro-esophageal junction (GEJ) and those aris ing in Barrett's esophagus (BE) are increasing in the West and have a poorer prognosis than distal stomach cancers. This has been attributed mainly to anatomical location, but biological factors such as growth- regulatory molecules have been implicated. We have investigated the ex pression of one of these factors, TGF alpha, and its precursor prepro TGF alpha in 82 adenocarcinomas of GEJ (32 resected specimens and 50 b iopsies) as well as in 48 BE biopsies without tumor, by immunohistoche mistry and by Western-blot analysis. TGF alpha staining was shown in t he cytoplasm and membrane of cells. Western blot confirmed that most i mmunoreactivity was against mature TGF alpha (5.6 kDa), but higher-mol ecular-weight bands were also identifiable, suggesting some reactivity with prepro protein. TGF alpha expression was more extense and intens e in intestinal metaplasia and cancer. The tubular histological type o f adenocarcinoma was more often positive than the signet-ring type. Pr imary tumors with lymph-node metastases also had increased TGF alpha e xpression. We conclude, therefore, that there is differential regulati on of the expression of TGF alpha and its precursors during esophageal tumorigenesis. (C) 1995 Wiley-Liss, Inc.