Altered Distribution of β-Catenin, and Its Binding Proteins E-Cadherin and APC, in Ulcerative Colitis–Related Colorectal Cancers

• Published in: Modern pathology 2001-01, Vol.14 (1), p.29-39
• Main Authors: Aust, Daniela E, Terdiman, Jonathan P, Willenbucher, Robert F, Chew, Karen, Ferrell, Linda, Florendo, Carmina, Molinaro-Clark, Annette, Baretton, Gustavo B, Löhrs, Udo, Waldman, Frederic M
• Format: Article
• Language: English
• Subjects: Adenomatous Polyposis Coli Protein; APC; beta Catenin; Cadherins - metabolism; Carcinoma - complications; Carcinoma - metabolism; Carcinoma - pathology; Cell Membrane - metabolism; Cell Membrane - pathology; Cell Nucleus - metabolism; Cell Nucleus - pathology; Colitis, Ulcerative - complications; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Colon - anatomy & histology; Colon - pathology; Colorectal cancer; Colorectal Neoplasms - complications; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cytoplasm - metabolism; Cytoplasm - pathology; Cytoskeletal Proteins - metabolism; E-cadherin; Female; Humans; Immunohistochemistry; Intestinal Mucosa - anatomy & histology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Laboratory Medicine; Male; Medicine; Medicine & Public Health; Neoplasm Proteins - metabolism; Neoplasm Staging; original-article; Pathology; Trans-Activators; Ulcerative colitis; β-catenin
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3880253

The β-catenin pathway plays a central role in transcriptional signaling and cell–cell interactions in colonic epithelium. Alterations of the expression of β-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 β-catenin pathway than sporadic cancers. To test this hypothesis, expres-sion and subcellular localization of β-catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related and 42 sporadic colorectal cancers. Although β-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 β-catenin and a decrease in cytoplasmic APC expression also were seen in both cancer groups compared with normal epithelium. Abnormal β-catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal β-catenin expression was more closely linked to APC alterations in sporadic cancers than in UC-related cancers. These data suggest that alterations of the β-catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of β-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.