Symposium: Molecular Genetics in Sarcoma

Clinical Orthopaedics and Related Research

, Volume 466, Issue 9, pp 2052-2059

Hypoxia Markers in Human Osteosarcoma: An Exploratory Study

  • Hiroo MizobuchiAffiliated withDepartment of Surgery, Memorial Sloan-Kettering Cancer Center
  • , José Manuel García-CastellanoAffiliated withDepartment of Surgery, Memorial Sloan-Kettering Cancer Center
  • , Shaji PhilipAffiliated withDivision of Hematology/Oncology, Department of Pediatrics, The Children’s Hospital at Montefiore
  • , John H. HealeyAffiliated withDepartment of Surgery, Memorial Sloan-Kettering Cancer Center
  • , Richard GorlickAffiliated withDivision of Hematology/Oncology, Department of Pediatrics, The Children’s Hospital at Montefiore Email author 

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Abstract

Neoplastic cells growing under hypoxic conditions exhibit a more aggressive phenotype by activating a cascade of molecular events partly mediated by hypoxia-inducible transcription factor (HIF-1α) and vascular endothelial growth factor (VEGF). The roles of these markers have been studied previously in several cancer lines. We ascertained the frequency of HIF-1α expression, VEGF expression, the degree of neovascularization, and cell proliferation in osteosarcoma samples. Samples from osteosarcoma patients were assessed for HIF-1α and VEGF protein expression using immunohistochemistry, neovascularization using antibodies for Factor VIII, and cell proliferation using the Ki-67 labeling index. Associations between these parameters and clinical features were examined. HIF-1α staining was positive in 35% of patients and metastases were present in 61% of these HIF-1α-positive patients. VEGF protein expression was detected in 69% of patients, 92% of whom were female. We observed an insignificant trend for a higher frequency of VEGF expression in the high-grade as compared to low-grade osteosarcoma. We observed no association between vascular density and proliferation index and any clinical parameters. We found an association between HIF-1α expression and metastatic disease and between VEGF expression and female gender.