Hepatocyte Antigen Expression in Barrett Esophagus and Associated Neoplasia

Hepatocyte antigen or hepatocyte paraffin 1 (Hep Par 1) is widely used as a diagnostic immunomarker for hepatocellular carcinoma. It has also been identified as a rate-limiting enzyme of the urea cycle, carbamoyl phosphate synthetase 1. Hep Par 1 has been detected in non-neoplastic small intestinal epithelium, but its expression in Barrett esophagus and its related neoplasia has not been well investigated. We immunohistochemically evaluated expression of Hep Par 1 on 75 cases of Barrett esophagus (25 cases without dysplasia, 16 cases with low-grade dysplasia, 25 cases with high-grade dysplasia, and 9 cases with intramucosal adenocarcinoma) on endoscopic biopsies and endoscopic mucosal resections. All 25 cases without dysplasia (100%) showed granular cytoplasmic Hep Par 1 staining (24 diffuse and 1 focal). Of the 16 cases with low-grade dysplasia, 12 (75%) were positive (5 diffuse and 7 focal), whereas 4 (25%) were negative (P=0.018). Of the 25 cases with high-grade dysplasia, 9 (36%) showed focal positivity, whereas 16 (64%) were negative (P=0.0001). Similarly of the 9 cases of intramucosal adenocarcinomas 3 (33%) were focally positive, whereas 6 (67%) were negative (P=0.0001). Hep Par 1 is diffusely expressed in non-neoplastic Barrett esophagus while it is frequently lost in related dysplasia and adenocarcinoma, suggesting decreased level of HepPar1 may represent an early event in Barrett-related tumor genesis. This warrants additional investigation to look for the possible role of carbamoyl phosphate synthetase 1 in the pathogenesis of Barrett-related neoplasia.