title: Giant cell tumors of the bone: molecular profiling and expression analysis of Ephrin A1 receptor, Claudin 7, CD52, FGFR3 and AMFR.
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.
authors.affiliation: Department of Pathology, University Hospital Charite, Schumannstrabe 20/21, D-10117 Berlin, Germany.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Guenther
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.forename: Anja
authors.initials: A
authors.lastname: Dankof
authors.forename: Ingo
authors.initials: I
authors.lastname: Melcher
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schaser
authors.forename: Hans-Udo
authors.initials: HU
authors.lastname: Kasper
authors.forename: Ralf-Jürgen
authors.initials: RJ
authors.lastname: Kuban
authors.forename: Ute
authors.initials: U
authors.lastname: Ungethüm
authors.forename: Christine
authors.initials: C
authors.lastname: Sers
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000074301:CD52 Antigen; D057167:Claudins; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D036082:Receptor, EphA1 / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000074301:CD52 Antigen; C000613862:CD52 protein, human; C473255:CLDN7 protein, human; D057167:Claudins; D006023:Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018121:Receptors, Cytokine; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; C496365:FGFR3 protein, human; D036082:Receptor, EphA1; D051498:Receptor, Fibroblast Growth Factor, Type 3