RESUMO
AIMS: Desmoid-type fibromatosis (DF) is a rare benign myofibroblastic neoplasm of the connective tissue that is unable to metastasize but is associated with a high local recurrence rate. Nuclear ß-catenin is the most commonly used histological marker of DF; however, clinical and biological predictive markers guiding the treatment and follow-up of DF are still lacking. Normally, ß-catenin is regulated by the cytoplasmic multiprotein complex of adenomatous polyposis coli (APC), axin, casein kinase 1α (CK1α), and glycogen synthase kinase 3ß (GSK-3ß); this phosphorylates and degrades ß-catenin, which would otherwise translocate to the nucleus. The aim of this study was to analyse the expression and localization of the ß-catenin-protein complex of the Wnt pathway in cells isolated from DF patients. METHODS AND RESULTS: We isolated cells from biopsies of DF patients, and demonstrated, by immunofluorescence and immunoblot analyses, that it is almost exclusively nuclear GSK-3ß that colocalizes and interacts with ß-catenin. The nuclear translocation of ß-catenin and GSK-3ß is not correlated with CTNNB1 mutations. In DF samples, the multiprotein complex is disrupted, as the cytoplasmic localization of APC and axin makes interaction with the nuclear ß-catenin and GSK-3ß impossible. CONCLUSIONS: Our data suggest that GSK-3ß is an additional DF marker with an important role in the aetiopathogenesis of this entity.
