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.
Bellei
Barbara
B
Laboratory of Histopathology, Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. b.bellei@libero.it
Pacchiarotti
Alberto
A
Perez
Marie
M
Faraggiana
Tullio
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000096:biosynthesis; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009182:Mycosis Fungoides / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D017730:Ki-1 Antigen; D015534:Trans-Activators; D051176:beta Catenin