Nuclear GSK-3[beta] segregation in desmoid-type fibromatosis

• Published in: Histopathology 2013-06, Vol.62 (7), p.1098
• Main Authors: Meneghello, Cristiana, Ousghir, Bouchra, Rastrelli, Marco, Anesi, Laura, Sommariva, Antonio, Montesco, Maria Cristina, Rossi, Carlo Riccardo, Hladnik, Uros, Segat, Daniela
• Format: Article
• Language: English
• Subjects: Beta; Colorectal cancer; Kinases
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12133

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 [beta]-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, [beta]-catenin is regulated by the cytoplasmic multiprotein complex of adenomatous polyposis coli (APC), axin, casein kinase 1[alpha] (CK1[alpha]), and glycogen synthase kinase 3[beta] (GSK-3[beta]); this phosphorylates and degrades [beta]-catenin, which would otherwise translocate to the nucleus. The aim of this study was to analyse the expression and localization of the [beta]-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-3[beta] that colocalizes and interacts with [beta]-catenin. The nuclear translocation of [beta]-catenin and GSK-3[beta] 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 [beta]-catenin and GSK-3[beta] impossible. Conclusions Our data suggest that GSK-3[beta] is an additional DF marker with an important role in the aetiopathogenesis of this entity. [PUBLICATION ABSTRACT]