Barrett's esophagus (BE) is a metaplastic change of the squamous esophageal 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
metaplasia and its relationship to
carcinogenesis. In this study, we investigated the potential of
villin, a cytoskeletal
protein, and
Ep-CAM, a glandular epithelial
glycoprotein, to serve as markers for enterocytic differentiation 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 microvilli by electron microscopy. By mapping of BE segments in 6 patients, correlations were also made between the histologic evidence of
metaplasia 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 patients 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 esophageal
metaplasia within the same patient. Mapping studies failed to reveal any correlation among histologic evidence of
metaplasia, dysplasia and
villin expression and confirmed the multifocal heterogeneity of
villin expression in BE. Preliminary data of 4
adenocarcinoma patients studied showed that
villin expression was absent in 3 and very low in 1 patient.
Ep-CAM was highly expressed in all
adenocarcinoma patients. Our results show that BE represents a complex epithelium with significant heterogeneity in
antigen expression and ultrastructural morphologic features. This molecular heterogeneity supports the presence of different stages of differentiation within the same epithelium.