Hypoxia Markers in Human Osteosarcoma: An Exploratory Study

  • Hiroo Mizobuchi
  • José Manuel García-Castellano
  • Shaji Philip
  • John H. Healey
  • Richard Gorlick
Symposium: Molecular Genetics in Sarcoma

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.

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Copyright information

© The Association of Bone and Joint Surgeons 2008

Authors and Affiliations

  • Hiroo Mizobuchi
    • 1
  • José Manuel García-Castellano
    • 1
  • Shaji Philip
    • 2
  • John H. Healey
    • 1
  • Richard Gorlick
    • 2
  1. 1.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Division of Hematology/Oncology, Department of PediatricsThe Children’s Hospital at MontefioreBronxUSA

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