E-Cadherin and β-Catenin Expression during Urothelial Carcinogenesis Induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in Mice

BACKGROUND: E-cadherin and β-catenin are adhesion molecules that promote integrity and stability of the urothelium. A decrease in theirexpression is associated with more aggressive tumour phenotypes with the ability to invade and metastasize. MATERIAL AND METHODS: 45 ICR male mice were used, of which 25 received N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05%) in drinking water for a period of 12 weeks. Immunohistochemical expression was evaluated in all urinary bladder preparations for E-cadherin and for β-catenin. RESULTS: Preneoplastic lesions showed staining patterns similar to normal urothelium. In simple and nodular hyperplasia, membrane staining was dominant (66.7-78.6 and 50-100%, respectively). In dysplasia a cytoplasmic pattern was prevalent (86.7-100%). Neoplastic lesions exhibit an abnormal staining pattern (100%) with heterogeneous staining (cytoplasmic, nuclear and membrane staining). A strong correlation was observed between both adhesion molecule staining patterns (r = 0.83; p = 0.039). CONCLUSIONS: In mice, as in humans, E-cadherin and β-catenin are valuable tools to investigate cellular adhesion status of urothelium and can be considered as indicators of tumour aggressiveness and evolution