Genetics Unit, 'Mauro Baschirotto' Institute for Rare Diseases, Vicenza, Italy.
Histopathology. 2013 Jun;62(7):1098-108. doi: 10.1111/his.12133. Epub 2013 Apr 24.
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 β-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, β-catenin is regulated by the cytoplasmic multiprotein complex of adenomatous polyposis coli (APC), axin, casein kinase 1α (CK1α), and glycogen synthase kinase 3β (GSK-3β); this phosphorylates and degrades β-catenin, which would otherwise translocate to the nucleus. The aim of this study was to analyse the expression and localization of the β-catenin-protein complex of the Wnt pathway in cells isolated from DF patients.
We isolated cells from biopsies of DF patients, and demonstrated, by immunofluorescence and immunoblot analyses, that it is almost exclusively nuclear GSK-3β that colocalizes and interacts with β-catenin. The nuclear translocation of β-catenin and GSK-3β 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 β-catenin and GSK-3β impossible.
Our data suggest that GSK-3β is an additional DF marker with an important role in the aetiopathogenesis of this entity.
韧带样纤维瘤病（DF）是一种罕见的良性结蹄组织肌纤维母细胞性肿瘤，无法转移，但局部复发率较高。β-连环蛋白是DF 最常用的组织学标志物；然而，目前仍缺乏指导 DF 治疗和随访的临床和生物学预测标志物。通常，β-连环蛋白受 APC、轴蛋白、酪蛋白激酶 1α（CK1α）和糖原合成酶激酶 3β（GSK-3β）组成的细胞质多蛋白复合物的调节；否则，β-连环蛋白会发生磷酸化和降解，从而易位到细胞核。本研究旨在分析来自 DF 患者的细胞中 Wnt 通路的β-连环蛋白蛋白复合物的表达和定位。
我们从 DF 患者的活检中分离出细胞，并通过免疫荧光和免疫印迹分析表明，几乎完全是核 GSK-3β 与β-连环蛋白共定位和相互作用。β-连环蛋白和 GSK-3β 的核易位与 CTNNB1 突变无关。在 DF 样本中，多蛋白复合物被破坏，因为 APC 和轴蛋白的细胞质定位使与核β-连环蛋白和 GSK-3β 的相互作用变得不可能。
我们的数据表明，GSK-3β 是 DF 的另一个标志物，在该实体的发病机制中具有重要作用。
