Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers Journal Article

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Authors: Horvai, A. E.; Roy, R.; Borys, D; O'Donnell, R. J.
Article Title: Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers
Abstract: The molecules Indian hedgehog (IHH), SP7 (also known as osterix), sex-determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and TWIST1 regulate the normal differentiation of osteo- and chondrogenic cells from precursors during skeletal development and remodeling. The aberrant function of the same molecules has been implicated in the pathogenesis of bone tumors. Preliminary studies suggest that antibodies against these molecules have practical, diagnostic or prognostic utility in tumors. However, a comprehensive analysis of the expression of these molecules in a large, diverse set of bone tumors has yet to be reported. The goals of this study were to compare the immunohistochemical profiles of IHH, SP7, SOX9, RUNX2 and TWIST1 among bone tumors and to determine the optimum panel for diagnostic utility. Tissue microarrays prepared from 206 undecalcified tumors (71 osteosarcomas, 26 osteoblastomas/osteoid osteomas, 50 giant cell tumors, 5 chondromyxoid fibromas and 54 chondroblastomas) were stained with antibodies to IHH, SP7, SOX9, RUNX2 and TWIST1. The stains were scored for intensity (0-3+) and distribution. The results were analyzed by cluster analysis. Optimum antibody panels for diagnostic sensitivity and specificity were calculated. Analysis revealed six main clusters that corresponded well to tumor types and suggested a close relationship between the stromal cells of giant cell tumor and the osteoblasts of osteosarcoma. The expression profile of chondromyxoid fibroma and chondroblastoma also suggested related differentiation. The distribution of osteoblastomas and osteoid osteomas was more heterogeneous. RUNX2, SOX9 and TWIST1 represented the most sensitive and specific immunohistochemical panel to distinguish among these diagnoses with the limitation that no result could discriminate between chondroblastoma and chondromyxoid fibroma. IHH and SP7 did not yield additional utility.
Journal Title: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Volume: 25
Issue: 11
ISSN: 1530-0285; 0893-3952
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 1452
End Page: 1461
Language: eng
DOI/URL:

10.1038/modpathol.2012.110

10.1038/modpathol.2012.110
Notes: JID: 8806605; 0 (Core Binding Factor Alpha 1 Subunit); 0 (Hedgehog Proteins); 0 (IHH protein, human); 0 (Nuclear Proteins); 0 (RUNX2 protein, human); 0 (SOX9 Transcription Factor); 0 (SOX9 protein, human); 0 (Sp7 protein, human); 0 (TWIST1 protein, human); 0 (Transcription Factors); 0 (Tumor Markers, Biological); 0 (Twist Transcription Factor); 2012/07/06 [aheadofprint]; ppublish