Nuclear accumulation of beta-catenin is a common and early event during neoplastic progression of Barrett esophagus

Our aim was to characterize expression and mutation of beta-catenin in the progression of Barrett esophagus to adenocarcinoma. Immunohistochemical ana lysis of beta-catenin was performed on paraffin-embedded tissue from 30 cas es with adenocarcinomas and premalignant lesions. To determine whether ther e is a correlation between beta-catenin nuclear accumulation and exon 3 mut ation of this gene, mutational analysis by polymerase chain reaction-single -strand conformation polymorphism was performed on DNA extracted from the s ame 30 adenocarcinomas. As a result, the prevalence of reduced expression o f beta-catenin on the membrane, with or without nuclear staining increased significantly from low-grade (LG) to high-grade (HG) dysplasia. Focal nucle ar staining for beta-catenin was present in 19 cases of adenocarcinoma, and nuclear staining was associated significantly with progression from metapl asia to LG dysplasia. In addition, in glands with clear histologic transiti on from metaplasia to LG dysplasia, nuclear accumulation of beta-catenin wa s found only in the LG dysplastic areas. No mutation in exon 3 of the beta- catenin gene was detected in adenocarcinomas. These results demonstrate tha t disturbance of the APC/beta-catenin pathway, as indicated by nuclear accu mulation of beta-catenin, is a common and early event during neoplastic pro gression in Barrett esophagus.