INCREASED IMMUNOREACTIVITY FOR RAB11, A SMALL GTP-BINDING-PROTEIN, INLOW-GRADE DYSPLASTIC BARRETTS-EPITHELIA

Adenocarcinoma of the esophagus develops from metaplastic Barrett's co lumnar epithelia through the evolution of dysplastic epithelial interm ediates. Although the role of dysplasia leading to adenocarcinoma is w ell established, far less is known regarding the cellular changes invo lved in this process. Because the development of dysplasia is characte rized by the loss of apical secretory specializations, we hypothesized that changes in apical trafficking might be involved in the dysplasti c process. We have sought to evaluate the expression of an important c andidate regulator of apical trafficking, the small GTP-binding protei n, Rab11, in resection and biopsy tissue from patients with Barrett's esophagus. Sections from esophageal resection specimens from 4 patient s and endoscopic biopsies from 60 patients were stained with antibodie s against Rab11 and Rab25 as well as protein markers of the Golgi appa ratus and p53 protein. Rab11 staining in low-grade dysplastic regions was similar to that observed with monoclonal antibodies against Rab25 and gamma-adaptin and colocalized with staining for the Golgi marker, the mannose-6-phosphate receptor. In the esophageal adenocarcinoma res ections, prominent Rab11 immunostaining was observed in the supranucle ar region of low-grade dysplastic cells. In contrast, regions of high- grade dysplasia demonstrating strong nuclear p53 staining showed only diffuse or absent Rab11 staining. In endoscopic biopsies, 91% of biops ies that were read unanimously as low-grade dysplasia demonstrated sup ranuclear Rab11 staining. Fourteen percent of biopsies unanimously gra ded as being without dysplasia demonstrated perinuclear Rab11 staining . No p53 immunostaining was observed in any of the low-grade dysplasia biopsy specimens. An increase in Rab11 immunoreactivity seems to corr elate with low-grade dysplasia, whereas p53 immunostaining correlates with high-grade dysplasia. The colocalization of Rab11 staining with i ncreased immunoreactivity for markers of the trans-Golgi system is con sistent with a defect in apical trafficking due to an expansion of eit her the trans-Golgi compartment or the apical recycling vesicle system .