Wnt pathway-related gene expression during malignant progression in ulcerative colitis

Long-standing ulcerative colitis (UC) has been associated with a high risk of developing colonic adenocarcinoma. Importantly, both low- and high-grade dysplasia are strongly related to the presence or development of malignancy. The canonical Wnt/beta-catenin signaling pathway is of crucial importance in cancer development and progression, but its role in UC-retated carcinogenesis remains to be determined. We evaluated the immunolabeling patterns of beta-catenin, as well as the products of Wnt-associated cancer genes E-cadherin, cyclin D1 and c-myc, along the dysplasia-carcinoma pathway in UC. For this purpose, immunohistochemistry (IHC) was performed on 18 adenocarcinomas and 17 dysplasias, derived from 21 patients. We found that intracellular beta-catenin accumutation, the hallmark of Wnt signating activation, is observed in dysptasia, together with enhanced labeling of nuclear protein cyclin D1 and reduction of membranous labeting of E-cadherin. c-myc displayed moderate immunotabeling in the (pre)malignant lesions. Thus, the Wnt pathway is activated in early stages of matignant progression in UC. Furthermore, upregulation of the oncogene cyclin D1 and clownregulation of tumor suppressor E-cadherin also occurs in the (pre)neoplastic state. This may contribute to the high potential for malignant degeneration of dysplasia in UC-retated colitis. (c) 2007 Elsevier GmbH. All rights reserved.