REDUCED EXPRESSION OF MOLECULES OF THE CADHERIN CATENIN COMPLEX IN THE TRANSITION FROM COLORECTAL ADENOMA TO CARCINOMA/

E-cadherin is crucial to the intercellular adherens junctions which al e involved in the organisation and maintenance of epithelial structure and suppression of tumour invasion. E-cadherin is associated with the actin cytoskeleton via cytoplasmic proteins, including alpha-, beta- and gamma-catenins, which together form the cadherin/catenin complex. To evaluate changes of the molecules of the cadherin/catenin complex i n colorectal carcinogenesis, seventy-foul sporadic adenomas, samples o f histologically normal epithelium adjacent to 65 adenomas, and 52 car cinomas arising in adenomas were investigated by immunohistochemistry. All normal epithelial cells showed a uniform membranous staining patt ern for E-cadherin, alpha-, beta-, and gamma-catenin. Decreased expres sion of all 4 proteins occurred in parallel in adenomas and carcinomas (in all cases, p<10(-5)). Decreased expression of the cadherin/cateni n complex ill adenomas was associated with increasing severity of dysp lasia (p<0.001, for E-cadherin, alpha-, and gamma-catenin, p<0.005 for beta-catenin). Carcinomas displayed significantly reduced expression of the cadherin/catenin complex compared with their associated adenoma s (all p<0.001). The results directly confirm that colorectal tumour p rogression and invasion is associated with disruption of the cadherin/ catenin complex and suggest that the genetic changes and transcription al modulation of catenins underlying this progression may affect all m embers of the complex.