title: Expression of cartilage growth plate signalling molecules in chondroblastoma.
abstract: Chondroblastoma (CB) is a rare benign tumour (<1% of all bone tumours) involving epiphyseal long bones (male:female 1.5:1). During development, and in the postnatal period, IHh/PTHrP and FGF signalling molecules control the space and timing of chondrocyte differentiation. Considering the close relationship of CB with the growth plate (age and location), the expression of proteins involved in epiphyseal growth regulation was studied. Twelve cases of CB were retrieved. Immunohistochemistry was performed using antibodies against fibroblast growth factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), FGFR-3, bcl-2, p21, parathyroid hormone-related peptide (PTHrP), and parathyroid hormone-related peptide receptor (PTHR1). Three observers evaluated haematoxylin and eosin (H&E)-stained and immunostained slides independently. Semi-quantitative estimation of the matrix, the type of matrix, and immunostaining was performed. Cellular and matrix-rich areas were evaluated separately. Diverse amounts and types of matrix were present in different tumours, as well as within individual tumours. Signalling molecules were expressed in 50-100% of the cases. Higher levels of expression were found in cellular areas than in matrix-rich areas, especially for PTHR1, bcl-2, and FGFR-3. CB is an unusual entity affecting specific sites, showing that both IHh/PTHrP and FGF signalling are active. Higher expression was found in cellular than in matrix-rich areas, as in the proliferating/pre-hypertrophic growth plate zone in comparison with the hypertrophic/calcifying zone. Previous studies have shown the same molecules to be expressed with a similar pattern in chondrosarcomas. The sum of the evaluated features indicates that CB is a neoplasm originating from a mesenchymal cell committed towards chondrogenesis via active growth plate signalling pathways.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Romeo
authors.forename: J V M G
authors.initials: JV
authors.lastname: Bovée
authors.forename: N A A
authors.initials: NA
authors.lastname: Jadnanansing
authors.forename: A H M
authors.initials: AH
authors.lastname: Taminiau
authors.forename: P C W
authors.initials: PC
authors.lastname: Hogendoorn
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002357:Cartilage Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002648:Child; D002804:Chondroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006132:Growth Plate / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D044162:Parathyroid Hormone-Related Protein / Q000032:analysis; D011505:Protein-Tyrosine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D044162:Parathyroid Hormone-Related Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D044168:Receptor, Parathyroid Hormone, Type 1; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3