Aberrant nuclear localization of β-catenin without genetic alterations in β-catenin or Axin genes in esophageal cancer

Abstract

BACKGROUND: beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma. MATERIALS AND METHODS: Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression. RESULTS: Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa. CONCLUSION: A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin.