Abstract
Giant cell tumors (GCTs) of the bone are osteolytic neoplasms with variable degrees of aggressiveness. The aim of this study was the molecular characterization of GCT tissue. We established gene expression profiles and discovered a number of genes that have not been described in GCTs before. RNA was prepared from 7 cryopreserved GCTs (primary tumors n = 5, relapses n = 2) and was hybridized to Affymetrix HG U133A microarrays. Paraffin-embedded samples were used for immunohistochemical validation (primary tumors n = 16, relapses n = 6). Gene ontology revealed that the majority of genes, found to be differentially expressed between primary and recurrent GCTs, were associated with receptor tyrosine kinase activity. We selected one upregulated gene (Claudin 7) and four downregulated genes (CD52, Ephrin A1 receptor, autocrine motility factor receptor [AMFR] and fibroblast growth factor receptor 3 [FGFR3] for further analysis using immunohistochemistry. Immunohistochemical analysis of CD52, AMFR, and Ephrin A1 receptor revealed expression profiles concordant with the microarray data, also with regard to differences between primary tumors and relapses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / metabolism
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / metabolism
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Bone Neoplasms / genetics*
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Bone Neoplasms / metabolism
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Bone Neoplasms / pathology
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CD52 Antigen
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Claudins
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Female
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Fluorescent Antibody Technique, Indirect
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic*
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Gene Expression*
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Giant Cell Tumor of Bone / genetics*
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Giant Cell Tumor of Bone / metabolism
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Giant Cell Tumor of Bone / pathology
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Glycoproteins / genetics
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Glycoproteins / metabolism
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Humans
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Immunoenzyme Techniques
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Middle Aged
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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RNA, Messenger / metabolism
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RNA, Neoplasm / analysis
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Receptor, EphA1 / genetics
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Receptor, EphA1 / metabolism
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Receptor, Fibroblast Growth Factor, Type 3 / genetics
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Receptor, Fibroblast Growth Factor, Type 3 / metabolism
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Receptors, Autocrine Motility Factor
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Receptors, Cytokine / genetics
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Receptors, Cytokine / metabolism
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Ubiquitin-Protein Ligases
Substances
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Antigens, CD
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Antigens, Neoplasm
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Biomarkers, Tumor
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CD52 Antigen
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CD52 protein, human
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CLDN7 protein, human
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Claudins
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Glycoproteins
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Membrane Proteins
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Cytokine
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AMFR protein, human
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Receptors, Autocrine Motility Factor
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Ubiquitin-Protein Ligases
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FGFR3 protein, human
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Receptor, EphA1
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Receptor, Fibroblast Growth Factor, Type 3