TGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone.
Eyden, Brian P
Prins, Frans A
Briaire-de Bruijn, Inge H
Taminiau, Antonie H M
Hogendoorn, Pancras C W
AffiliationDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
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AbstractChondromyxoid fibroma (CMF) is a rare benign cartilaginous bone tumour with a lobular architecture containing stellate and myofibroblast-like spindle cells. The aim of this study was to investigate the presence, spatial distribution, and extent of myoid differentiation in CMF and to evaluate a possible causative role for TGF-beta1 signalling, which is known to promote smooth muscle actin (SMA) expression. Twenty cases were studied for immunoreactivity for muscle-specific actin (MSA), SMA, desmin, h-caldesmon, calponin, TGF-beta1, and plasminogen activator inhibitor type 1 (PAI-1). The extent of myofibroblastic differentiation was further investigated ultrastructurally, including immuno-electron microscopy using antibodies against MSA and SMA, focusing upon the different cell types in CMF. The expression of potential genes driving this process was quantified by Q-RT-PCR (TGF-beta1, fibronectin, its EDA splice variant, and PAI-1). Tumour cells, especially those with a spindled morphology, showed diffuse immunoreactivity for MSA, SMA, TGF-beta1, and PAI-1, while desmin, h-caldesmon, and calponin were absent. Ultrastructurally, neoplastic cells showed the presence of myofilaments and rare dense bodies, which were more prominent in spindle cells and less so in chondroblast-like cells. Immuno-electron microscopy confirmed the actin nature of these myofilaments. No fibronexus was identified. The functional activity of TGF-beta1 was demonstrated by the identification of PAI-1, a related downstream molecule both immunohistochemically as well as by Q-RT-PCR. There was a linear correlation between TGF-beta1 and PAI-1 expression. Fibronectin-EDA levels were low. We have therefore substantiated the presence of morphological, immunohistochemical, and immuno-electron microscopic partial myofibroblastic differentiation in CMF, driven by TGF-beta1 signalling.
CitationTGF-beta1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone. 2006, 208 (1):26-34 J. Pathol.
JournalThe Journal of Pathology