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Aberrant expression of the human epidermal growth factor receptor 2 oncogene is not a common feature in osteosarcoma
Authors:Baumhoer Daniel  Smida Jan  Specht Katja  Bink Karin  Quintanilla-Martinez Leticia  Rosemann Michael  Siggelkow Heide  Nathrath Walter B J  Atkinson Michael J  Bielack Stefan  Jundt Gernot  Nathrath Michaela
Affiliation:
  • a Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland
  • b Bone Tumour Reference Center at the Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland
  • c Clinical Cooperation Group Osteosarcoma, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany
  • d Department of Pediatrics, Technische Universitaet Muenchen and Pediatric Oncology Center, 80804 Munich, Germany
  • e Institute of Pathology, Technische Universitaet Muenchen, 81675 Munich, Germany
  • f Institute of Pathology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany
  • g Institute of Radiation Biology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany
  • h University Medical Center Goettingen, Department for Gastroenterology and Endocrinology and Endokrinologikum, 37075 Goettingen, Germany
  • i Institute of Pathology, Klinikum München-Harlachingen, 81545 Munich, Germany
  • j Klinikum Stuttgart Olgahospital, Pediatrics 5—Oncology, Hematology, Immunology, 70176 Stuttgart, Germany
  • Abstract:
    Human epidermal growth factor receptor 2 expression in osteosarcoma and its relationship to prognosis have been the subject of several conflicting reports, most of them relying on immunohistochemical studies. Because the urgent need of prognostic markers and effective new treatment options for osteosarcoma patients, we evaluated the role of human epidermal growth factor receptor 2 in 2 well-characterized sets of pretherapeutic osteosarcoma samples (46 paraffin-embedded and 46 fresh-frozen biopsy samples) using immunohistochemistry with 2 different antibodies [DAKO A0485 (Glostrup, Denmark) and Novocastra CB11 (Newcastle, UK)] as well as fluorescence in situ hybridization, real-time polymerase chain reaction, and SNP array analyses and correlated our findings with clinicopathological parameters. However, our study failed to detect unequivocal evidence of human epidermal growth factor receptor 2 gene amplification or overexpression of human epidermal growth factor receptor 2 messenger RNA or protein in any of the investigated tumors. Only in a small subset of samples, a moderate increase in messenger RNA levels (13.6%) or focal membranous immunoreactivity (8.7%; A0485) was detected but did not correlate with survival or response to chemotherapy. Cytoplasmic staining was identified more frequently (63%; CB11) but again did not show any association with clinicopathological parameters. In conclusion, our study does not support a role for human epidermal growth factor receptor 2 as a prognostic marker in osteosarcoma.
    Keywords:Osteosarcoma   HER-2/neu   ERBB2   FISH   Immunohistochemistry   qRT-PCR   Single nucleotide polymorphism (SNP) array
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