MULTIFOCAL HETEROGENEITY IN VILLIN AND EP-CAM EXPRESSION IN BARRETTS-ESOPHAGUS

Barrett's esophagus (BE) is a metaplastic change of the squamous esoph ageal epithelium to columnar gastric or intestinal-like epithelium. BE is associated with long-standing gastroesophageal reflux disease and carries an increased risk for dysplasia and adenocarcinoma. Little if any is known regarding the differentiation state of esophageal metapla sia and its relationship to carcinogenesis. In this study, we investig ated the potential of villin, a cytoskeletal protein, and Ep-CAM, a gl andular epithelial glycoprotein, to serve as markers for enterocytic d ifferentiation in BE at the molecular level. Endoscopic mucosal biopsy samples of normal esophagus, BE, stomach and duodenum were collected from 23 patients with BE. Biopsies were analyzed for villin and Ep-CAM expression by immunoblotting, and in some cases for the presence of m icrovilli by electron microscopy. By mapping of BE segments in 6 patie nts, correlations were also made between the histologic evidence of me taplasia and villin expression. Villin was uniformly expressed in all duodenal samples but was not detected in normal esophagus and stomach. In BE biopsies, villin expression was limited to the subset: of patie nts whose adjacent biopsies showed microvilli by electron microscopy. In several patients studied, however, the expression of villin and the epithelial glycoprotein Ep-CAM differed among various regions of esop hageal metaplasia within the same patient. Mapping studies failed to r eveal any correlation among histologic evidence of metaplasia, dysplas ia and villin expression and confirmed the multifocal heterogeneity of villin expression in BE, Preliminary data of 4 adenocarcinoma patient s studied showed that villin expression was absent in 3 and very low i n I patient. Ep-CAM was highly expressed in all adenocarcinoma patient s. Our results show that BE represents a complex epithelium with signi ficant heterogeneity in antigen expression and ultrastructural morphol ogic features. This molecular heterogeneity supports the presence of d ifferent stages of differentiation within the same epithelium. (C) 199 6 Wiley-Liss, Inc.