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

ABSTRACT

The majority of the adenocarcinomas arising in Barrett esophagus manifest clinically at an advanced stage and have a poor prognosis. As a result of this, much attention has been directed toward the exploration of markers for neoplastic progression in Barrett esophagus. The objective of the present study was to evaluate the role of beta-catenin expression in the progression of Barrett esophagus to adenocarcinoma by immunohistochemical analysis in 25 cases with adenocarcinoma and premalignant lesions and to examine its relationship to various prognostic factors. In our study, abnormal beta-catenin expression consisting of the loss of membranous staining and the appearance of the nuclear staining was found in 23 cases of esophageal adenocarcinoma [92%]. Of patients with the 23 tumors showing abnormal beta-catenin expression. 16 cases [64%] nuclear staining was present. This nuclear reaction was associated significantly with progression from metaplasia to low-grade dysplasia [P = 0.01]. In addition, in glands with clear histological transition from metaplasia to low-grade dysplasia. focal nuclear accumulation of beta-catenin was found only in the low-grade dysplastic areas. Also, we proved that the prevalence of reduced expression of beta-catenin on the membrane with or without nuclear staining increased significantly from low-grade to high-grade dysplasia to adenocarcinoma [P > 0.05]. According to clinicopathological correlation, abnormal beta-catenin expression was highly expressed in high grade tumors [G[3]] and tumors with lymph node metastasis with equal incidence 100%. Also, we found no gross difference in beta-catenin expression between Tis-T[1] and T[2]-T[3] tumors. 88.9% and 93.75%. respectively. These results indicate that abnormal expression of beta-catenin is a common and early event during neoplastic progression in Barrett esophagus and could be a valuable prognostic marker. Also it could be used to identify patients with Barrett esophagus who run a high risk of disease progression