Identification of intestinal-type Barrett's metaplasia by using the intestine-specific protein villin and esophageal brush cytology

Villin is an actin-binding cytoskeletal protein required for brush-border f ormation in the normal small intestinal and renal proximal tubule epitheliu m. Villin is a marker of cell differentiation in small intestinal and renal cell lineages, and recent studies have shown villin to be highly expressed in 100% of intestinal-type Barrett's metaplasias. This epithelium is the s ingle greatest risk factor for developing esophageal adenocarcinoma and ari ses when the normal esophageal squamous epithelium is replaced by a small i ntestine-like columnar epithelium after damage by chronic gastroesophageal reflux. in intestinal-type Barrett's metaplasia, the villin protein exhibit s a highly characteristic staining pattern in which strong apical, brush-bo rder staining of columnar epithelial cells is observed. In this study, the ability to identify intestinal metaplastic cells by using this distinct vil lin staining pattern was examined in endoscopic esophageal brushings from p atients with confirmed Barrett's metaplasia. Esophageal brushings from 81% (17 of 21) of patients with Barrett's metaplasia demonstrated individual co lumnar cells with the characteristic villin staining pattern, whereas all n ormal esophageal squamous cells, blood cells, and gastric columnar cells we re negative for villin expression. Northern blot analysis demonstrated vill in mRNA expression in Barrett's metaplasia but not in the normal squamous e sophagus or gastric mucosa from the same patients. The combined use of vill in immunohistochemical analysis and esophageal brush cytology may provide a simple and effective method of detecting intestinal-type Barrett's metapla sia in patients at higher risk for developing this epithelium, such as thos e experiencing chronic gastroesophageal reflux symptoms. Mol. Carcinog. 24: 137-143, 1999. (C) 1999 Wiley-Liss, Inc.