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TGF‐β1 drives partial myofibroblastic differentiation in chondromyxoid fibroma of bone
Author(s) -
Romeo Salvatore,
Eyden Brian,
Prins Frans A,
Briairede Bruijn Inge H,
Taminiau Antonie HM,
Hogendoorn Pancras CW
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1887
Subject(s) - calponin , caldesmon , desmin , myofibroblast , pathology , osteopontin , biology , chemistry , actin , microbiology and biotechnology , immunohistochemistry , fibrosis , vimentin , endocrinology , medicine , calmodulin , biochemistry , enzyme
Chondromyxoid 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‐β1 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‐β1, 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‐ β 1 , fibronectin, its EDA splice variant, and PAI‐1 ). Tumour cells, especially those with a spindled morphology, showed diffuse immunoreactivity for MSA, SMA, TGF‐β1, 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‐β1 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‐ β 1 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‐β1 signalling. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.