S1064 Evaluation of Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) in Esophageal Adenocarcinoma in Barrett's Esophagus

Abstract

Background:Epithelial mesenchymal transition(EMT) is a crucial event in the metastatisis of carcinoma. EMT enables epithelial tumors to invade into the mesenchymal submucosa. The key feature of EMT is E-cadherin down-regulation. Snail, Slug and Twist are well recognized transcriptional factors as repressors of E-cadherin expression. Recently, a direct link has been shown between the EMT and cancer stem cell(CSC). CSC has the ability to self-renew and continually sustain tumorigenesis. Cells undergoing an EMT could be the precursors to metastatic carcinoma, perhaps as CSCs. CD133 is recognized marker for gastrointestinal CSCs. Aim:To characterize expressions of Snail, Slug, Twist and CD133 in the metastatic esophageal adenocarcinoma(EAC) in Barrett's esophagus(BE). Method:Formalin-fixed, paraffin embedded specimens of surgically treated early EAC were used. All slides were first reviewed by a well experienced GI pathologist, then were immunohistochemically stained for primary antibodies to Snail, Slug, Twist and CD133. We assessed if invading edges of tumor in the submucosa were stained for each antibody, and if there were differences of intensity of staining between in intramucosal cancer cells and in submucosal metastatic cells. The slides were scored by (1) intensity of staining (0=negative, 1=weak, 2=moderate, 3= intense);(2) percentage of epithelial cells staining (0=0-5%, 1=6-25%, 2=26-50%, 3=5175%, 4=76-100%);(3) percentage of invading cancer cells staining (same as epithelial cells). Cellular localization (nuclear, cytoplasm, cell surface) and uniformity (focal, general) were also assessed. Result:10 patients were analyzed. All four proteins were expressed in the cancers with uniform staining in both the mucosa and submucosa with Snail being more localized in the nucleus while Slug, Twist and CD133 were exclusively in the cytoplasm. Intensity of staining of metastatic cancer cells in submucosa was similar to those in the mucosa. Semi-quantitative scored analyses of Snail, Slug, Twist and CD133 for overall intensity were 2.5, 2.8, 1.9, and 2.4, respectively. For epithelial tumor cells, the scores were 4.0, 3.8, 3.3, and 3.2, respectively, whereas for invading metastatic cells, 4.0, 3.6, 3.1, and 3.6. Conclusion:This is the first report assessing the expression of known E-cadherin repressors, Snail, Slug, Twist and CSC marker, CD133 in the development of EAC in BE. All invading edges of tumor were found to abundantly express Snail, Slug, Twist and CD133 suggesting that unlike late staged cancers, early staged cancers are predominantly made of cells with metastatic potential which emphasizes the need to completely remove these early cancers.