title: Genetic Analysis of Giant Cell Lesions of the Maxillofacial and Axial/Appendicular Skeletons.
abstract: OBJECTIVE
  To compare the genetic and protein expression of giant cell lesions (GCLs) of the maxillofacial (MF) and axial/appendicular (AA) skeletons. We hypothesized that when grouped according to biologic behavior and not simply by location, MF and AA GCLs would exhibit common genetic characteristics.
  
  
  METHODS
  This was a prospective and retrospective study of patients with GCLs treated at Massachusetts General Hospital from 1993 to 2008. In a preliminary prospective study, fresh tissue from 6 aggressive tumors each from the MF and AA skeletons (n = 12 tumors) was obtained. RNA was extracted and amplified from giant cells (GCs) and stromal cells first separated by laser capture microdissection. Genes highly expressed by GCs and stroma at both locations were determined using an Affymetrix GeneChip analysis. As confirmation, a tissue microarray (TMA) was created retrospectively from representative tissue of preserved pathologic specimens to assess the protein expression of the commonly expressed genes found in the prospective study. Quantification of immunohistochemical staining of MF and AA lesions was performed using Aperio image analysis to determine whether immunoreactivity was predictive of aggressive or nonaggressive behavior.
  
  
  RESULTS
  Five highly ranked genes were found commonly in GCs and stroma at each location: matrix metalloproteinase-9 (MMP-9), cathepsin K (CTSK), T-cell immune regulator-1 (TCIRG1), C-type lectin domain family-11, and zinc finger protein-836. MF (n = 40; 32 aggressive) and AA (n = 48; 28 aggressive) paraffin-embedded tumors were included in the TMA. The proteins CTSK, MMP-9, and TCIRG1 were confirmed to have abundant expression within both MF and AA lesions. Only the staining levels for TCIRG1 within the GCs predicted the clinical behavior of the MF lesions.
  
  
  CONCLUSIONS
  MMP-9, CTSK, and TCIRG1 are commonly expressed by GCLs of the MF and AA skeletons. This supports the hypothesis that these lesions are similar but at different locations. TCIRG1 has not been previously associated with GCLs and could be a potential target for molecular diagnosis and/or therapy.
authors.affiliation: Assistant Professor, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, MA. Electronic address: zpeacock@partners.org.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Peacock
authors.affiliation: Assistant Professor, Department of Orthopaedics, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Schwab
authors.affiliation: Associate Professor, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: William C
authors.initials: WC
authors.lastname: Faquin
authors.affiliation: Associate Professor, Department of Orthopaedics, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Former Fellow, Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Benita
authors.affiliation: Assistant Professor, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: David H
authors.initials: DH
authors.lastname: Ebb
authors.affiliation: Walter Guralnik Distinguished Professor, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, MA.
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Kaban
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008441:Maxillary Neoplasms / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D012189:Retrospective Studies; D017154:Stromal Cells / Q000473:pathology; D046888:Tissue Array Analysis