Frequent beta-catenin overexpression without exon 3 mutation in cutaneous lymphomas.

Beta-catenin is a ubiquitously cytoplasmic protein that has a critical role in embryonic development and mature tissue homeostasis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Mutations that alter specific beta-catenin residues important for GSK-3beta phosphorylation, or increase the half-life of the protein, were identified in human cancer. However, the role of the Wnt pathway in B- and T-cell oncogenesis has not been extensively investigated. To assess the role of beta-catenin defects in primary cutaneous lymphomas, we examined the expression pattern and the genetic alteration of beta-catenin on 79 samples from 74 patients with primary cutaneous lymphomas from B- and T-cell origin. Immunohistochemical analysis revealed beta-catenin deregulation in five primary cutaneous B-cell lymphomas (21%) and in 21 primary cutaneous T-cell lymphomas (42%) without nuclear accumulation suggesting that activation and accumulation of beta-catenin may play an important role in the development of skin lymphomas. Mutation analysis of beta-catenin exon 3, which included the responsible element for Wnt signaling, was therefore done in 19 samples. However, genetic alterations of beta-catenin exon 3 were not detected in any of these cases suggesting that other regulatory mechanisms may be relevant in activating beta-catenin signaling in cutaneous lymphomas.