Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers

The beta -catenin pathway plays a central role In transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expre ssion of beta -catenin, and its binding partners E-cadherin and the adenoma tous polyposis coli protein (APC), are frequent events in sporadic colorect al cancer. Ulcerative colitis (UC)-related cancers originate in a field of chronic inflammation and therefore may have different alterations in the be ta -catenin pathway than sporadic cancers. To test this hypothesis, express ion and subcellular localization of beta -catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related a nd 42 sporadic colorectal cancers. Although beta -catenin and E-cadherin ex pression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both tumor groups showed an overall shift from membrano us to cytoplasmic expression for these proteins. An increase in nuclear loc alization of beta -catenin and a decrease in cytoplasmic APC expression als o were seen in both cancer groups compared with normal epithelium, Abnormal beta -catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal beta -catenin expression was more closely linked to APC alterations in sporadic cancers than in UC-related cancers. These data suggest that alterations of the beta -catenin pathway are important in both UC-related and sporadic co lorectal cancers. However, differences in the expression patterns of beta - catenin, E-cadherin, and APC between UC-related and sporadic colorectal can cers suggest that the specific alterations in this pathway may differ in th ese two cancer groups.