title: A tissue microarray study of osteosarcoma: histopathologic and immunohistochemical validation of xenotransplanted tumors as preclinical models.
abstract: BACKGROUND
  Osteosarcomas (OS) are aggressive neoplasms with a wide range of morphologic patterns.
  
  
  METHODS
  OS cases (primary and xenotransplanted) with paraffin blocks available were collected and included in tissue microarrays (TMAs). A morphologic evaluation including the different passages in mice was carried out according to the new WHO criteria. In addition, TMAs were analyzed with a wide panel of immunohistochemical (IHC) markers (osteonectin, osteocalcin,cytokeratin, S100, Sox-9, Ki-67, Bcl-2, p53, p16, survivin, CD99, and caveolin-1).
  
  
  RESULTS
  A total of 61 cases were collected. The distribution of the cases according to the histopathologic pattern was: 38 osteogenic OS, 8 primary chondrogenic OS, 2 primary telangiectatic OS, 6 parosteal OS, 2 primary small cell OS, 2 primary poorly differentiated OS, 1 primary dedifferentiated OS, and 3 primary pleomorphic MFH-like OS. The tumor morphology in xenotransplants was similar to the primary or metastatic tumor of origin and was generally maintained over the passages. The IHC results were heterogeneous and osteonectin and osteocalcin were the most expressed in original tumor and xenografts. S100 and Sox-9 were expressed in chondrogenic areas. Caveolin and survivin showed significant IHC variation between the subsequent passages. p16 displayed heterogenic expression. p53 expression increased over the passages, and Ki-67 expression was not associated with a more undifferentiated pattern, but increased over the passages.
  
  
  CONCLUSIONS
  An accurate morphologic evaluation using TMAs in original tumor is essential for the OS diagnosis; hence there is no IHC marker that alone distinguishes the OS subtypes. Xenografts in OS allow the study of tumor progression in this type of aggressive neoplasm.
authors.affiliation: Department of Pathology, University of Valencia, Valencia, Spain.
authors.forename: Empar
authors.initials: E
authors.lastname: Mayordomo
authors.forename: Isidro
authors.initials: I
authors.lastname: Machado
authors.forename: Francisco
authors.initials: F
authors.lastname: Giner
authors.forename: Stine H
authors.initials: SH
authors.lastname: Kresse
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.forename: Carmen
authors.initials: C
authors.lastname: Carda
authors.forename: Samuel
authors.initials: S
authors.lastname: Navarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005240:Feasibility Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis / Q000379:methods; D015675:Osteocalcin / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D015676:Osteonectin; D015675:Osteocalcin