Frequent β-catenin overexpression without exon 3 mutation in cutaneous lymphomas

β-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 β-catenin residues important for GSK-3β 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 β-catenin defects in primary cutaneous lymphomas, we examined the expression pattern and the genetic alteration of β-catenin on 79 samples from 74 patients with primary cutaneous lymphomas from B- and T-cell origin. Immunohistochemical analysis revealed β-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 β-catenin may play an important role in the development of skin lymphomas. Mutation analysis of β-catenin exon 3, which included the responsible element for Wnt signaling, was therefore done in 19 samples. However, genetic alterations of β-catenin exon 3 were not detected in any of these cases suggesting that other regulatory mechanisms may be relevant in activating β-catenin signaling in cutaneous lymphomas.