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Increased
Immunoreactivity for Rab11, a Small GTP-Binding Protein, in Low-Grade Dysplastic
Barrett's Epithelia |
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Gregory S.
Ray, Jeffrey R. Lee, Kingsley Nwokeji, Luther R. Mills, and James R. Goldenring
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Departments
of Medicine, Surgery, and Cellular Biology and Anatomy (GSR, KN, JRG), and
Pathology (JRL, LRM), Institute for Molecular Medicine and Genetics, Medical
College of Georgia, and Augusta Veterans Affairs Medical Center, Augusta,
Georgia |
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Adenocarcinoma of the esophagus
develops from metaplastic Barrett's columnar epithelia through the evolution
of dysplastic epithelial intermediates. Although the role of dysplasia leading
to adenocarcinoma is well established, far less is known regarding the cellular
changes involved in this process. Because the development of dysplasia is
characterized by the loss of apical secretory specializations, we hypothesized
that changes in apical trafficking might be involved in the dysplastic process.
We have sought to evaluate the expression of an important candidate regulator
of apical trafficking, the small GTP-binding protein, Rab11, in resection
and biopsy tissue from patients with Barrett's esophagus. Sections from
esophageal resection specimens from 4 patients and endoscopic biopsies from
60 patients were stained with antibodies against Rab11 and Rab25 as well
as protein markers of the Golgi apparatus 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 resections, prominent Rab11 immunostaining was observed in
the supranuclear 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 biopsies
that were read unanimously as low-grade dysplasia demonstrated supranuclear
Rab11 staining. Fourteen percent of biopsies unanimously graded 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 correlate with low-grade dysplasia, whereas
p53 immunostaining correlates with high-grade dysplasia. The colocalization
of Rab11 staining with increased immunoreactivity for markers of the trans-Golgi
system is consistent with defect in apical trafficking due to an expansion
of either the trans-Golgi compartment or the apical recycling vesicle system.
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