Villin is an actin-binding cytoskeletal
protein required for brush-border formation in the normal small intestinal and renal proximal tubule epithelium.
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 single greatest risk factor for developing esophageal
adenocarcinoma and arises when the normal esophageal squamous epithelium is replaced by a small intestine-like columnar epithelium after damage by chronic
gastroesophageal reflux. In intestinal-type Barrett's
metaplasia, the
villin protein exhibits a highly characteristic staining pattern in which strong apical, brush-border staining of columnar epithelial cells is observed. In this study, the ability to identify intestinal metaplastic cells by using this distinct
villin staining pattern was examined in endoscopic esophageal brushings from patients with confirmed Barrett's
metaplasia. Esophageal brushings from 81% (17 of 21) of patients with Barrett's
metaplasia demonstrated individual columnar cells with the characteristic
villin staining pattern, whereas all normal esophageal squamous cells, blood cells, and gastric columnar cells were negative for
villin expression. Northern blot analysis demonstrated
villin mRNA expression in Barrett's
metaplasia but not in the normal squamous esophagus or gastric mucosa from the same patients. The combined use of
villin immunohistochemical analysis and esophageal brush cytology may provide a simple and effective method of detecting intestinal-type Barrett's
metaplasia in patients at higher risk for developing this epithelium, such as those experiencing chronic
gastroesophageal reflux symptoms.