Trefoil Factor Expression in a Human Model of the Early Stages of Barrett’s Esophagus

Background Trefoil proteins are believed to have an important role in mucosal protection and repair in the gastrointestinal tract. They are well recognized in Barrett’s esophagus and considered a potential biomarker for the condition. Metaplasia occurring in the esophageal remnant after esophagectomy is a human model for the early stages of development of Barrett’s esophagus. Aims To assess expression of trefoil proteins in post-esophagectomy columnar epithelium and to use trefoils as a molecular tool to understand regenerative mucosa in the esophagus. Methods Patients with columnar metaplasia in the esophageal remnant were recruited from a large esophago-gastric cancer center. Trefoil factor expression was determined using immunohistochemical techniques. Results Samples were obtained from 37 patients. TFF1 and TFF2 were expressed by all samples in a similar pattern to that described in studies of sporadic Barrett’s esophagus. TFF3 was less widely expressed and was significantly associated with time elapsed between surgery and endoscopy. Median time from surgery to endoscopy was 8.1 years for patients with TFF3 expression versus 3.4 years for those without (p = 0.004). Conclusions Widespread expression of trefoils in this environment suggests that these proteins have an important role in development of Barrett’s metaplasia. TFF3 expression may be absent in the early stages of metaplasia and may represent more established columnar epithelium. Biopsy samples from post-esophagectomy patients provide a valuable resource to study the early stages of Barrett’s esophagus.