Rab11 in dysplasia of Barrett's epithelia.

Abstract

Barrett's esophagus predisposes affected patients to the development of esophageal adenocarcinoma. The development of adenocarcinoma proceeds along a progression through low- and high-grade dysplasia. Surveillance of Barrett's patients requires serial endoscopic investigations and grading mucosal biopsies. Unfortunately, grading of biopsies by conventional hematoxylin and eosin staining is fraught with significant interobserver variations. We have found in both biopsy and resection specimens that immunostaining for the small GTP binding protein Rab11 is increased in low-grade dysplastic cells. This staining is lost in high-grade dysplastic cells. These results suggest that low-grade dysplastic cells undergo an apical trafficking blockade, which is released as cells progress to the less differentiated phenotype of high-grade dysplasia and adenocarcinoma. Examination of the SKGT-4 esophageal adenocarcinoma cell line demonstrated prominent mRNA and protein expression for Rab11. Rab11 immunostaining was present in SKGT-4 cells as a perinuclear nidus of punctate staining along with a more diffuse punctate pattern. Thus, Rab11 expression was present in a esophageal adenocarcinoma cells in culture. Markers of vesicle trafficking may be critical factors for grading of mucosal dysplastic transitions leading to adenocarcinoma.