The
beta-catenin pathway plays a central role in transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expression of
beta-catenin, and its binding partners
E-cadherin and the
adenomatous polyposis coli protein (APC), are frequent events in sporadic
colorectal cancer.
Ulcerative colitis (UC)-related
cancers originate in a field of chronic
inflammation and therefore may have different alterations in the
beta-catenin pathway than sporadic
cancers. To test this hypothesis, expression and subcellular localization of
beta-catenin,
E-cadherin, and APC were detected by immunohistochemistry in
paraffin sections from 33 UC-related and 42 sporadic
colorectal cancers. Although
beta-catenin and
E-cadherin expression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both
tumor groups showed an overall shift from membranous to cytoplasmic expression for these
proteins. An increase in nuclear localization of
beta-catenin and a decrease in cytoplasmic APC expression also 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
colorectal cancers. However, differences in the expression patterns of
beta-catenin,
E-cadherin, and APC between UC-related and sporadic
colorectal cancers suggest that the specific alterations in this pathway may differ in these two
cancer groups.