The Pattern of beta-Catenin Expression in Adenomas and Carcinomas of the Gallbladder

ABSTRACT

PURPOSE: beta-catenin is a key regulator of the cadherin-mediated cell adhesion system and also plays a role as a transcription regulating factor. Nuclear expression and mutation of beta-catenin have been identified in some benign and malignant tumors, and over expression of beta-catenin indicates an oncogenic potential. This study was designed to clarify the role of beta-catenin in the histogenesis of gallbladder carcinoma. METHODS: In benign hyperplastic lesions, adenomas, and carcinomas of the gallbladder, intracellular expression of beta-catenin was investigated by immunohistochemical stainings. Cyclin D1 and Ki-67 were also examined. RESULTS: All of the hyperplastic lesions showed membranous expression of beta-catenin. Adenomas and polypoid carcinomas showed significantly higher incidence of cytoplasmic and nuclear expression of beta-catenin than hyperplastic lesions and infiltrative carcinomas (P<0.01). Loss of beta-catenin expression was frequently noticed in infiltrative and poorly differentiated carcinomas. Nuclear expression of beta-catenin in carcinomas had unique pathologic characteristics, including polypoid growing, well differentiated tubular type, and early stage. Cytoplasmic and nuclear expression of beta-catenin showed good correlations with cyclin-D1 expression (P<0.05). The Ki-67 index was significantly higher in infiltrative carcinomas than in adenomas or polypoid carcinomas (P<0.05). CONCLUSION: Our results suggest that beta-catenin as a molecular marker may play a role in the carcinogenesis of the adenoma-carcinoma sequence of polypoid carcinomas. Infiltrative carcinomas, however, may have different mechanisms.