title: Chondromyxoid fibroma resembles in vitro chondrogenesis, but differs in expression of signalling molecules.
abstract: Chondromyxoid fibroma is a rare benign cartilaginous bone tumour characterized by morphological features that resemble different steps of chondrogenesis in terms of both cellular morphology, ranging from spindled to rounded cells, and the extracellular matrix formed, which ranges from fibrous to cartilaginous. The presence in chondromyxoid fibroma of signalling molecules that regulate the spatial expression of proteins involved in normal cartilage proliferation and differentiation was investigated in samples from 20 patients and compared with articular chondrocytes from 11 normal donors cultivated in 3D pellet culture. Sections were stained with safranin-O and H&E, and immunohistochemistry was performed for p16, cyclin D1, FGFR3, BCL2, p21, PTHLH, PTHR1 and N-cadherin. Expression patterns were analysed using hierarchical clustering. In chondromyxoid fibroma, specific morphological features correlated with a distinct pattern of expression. Comparison with normal chondrocytes in pellet culture showed a striking morphological resemblance, but with an unmistakably different pattern of expression. N-cadherin, PTHLH, and PTHR1 were expressed to a significantly higher level (p < 0.01) in articular chondrocyte pellets but, conversely, there was significantly lower expression of cyclin D1, p16 and BCL2 (p < 0.05) in these cells. Morphological similarities reflect common steps in cartilage differentiation, albeit driven by different molecular mechanisms. The proteins we have found to be differentially expressed seem crucial for neoplastic chondrogenesis.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Romeo
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Grogan
authors.forename: Antonie H M
authors.initials: AH
authors.lastname: Taminiau
authors.forename: Paul H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: Pierre
authors.initials: P
authors.lastname: Mainil-Varlet
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002358:Cartilage, Articular / Q000166:cytology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002804:Chondroblastoma / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins