Clinical Orthopaedics and Related Research

, 466:2052

Hypoxia Markers in Human Osteosarcoma: An Exploratory Study

Authors

  • Hiroo Mizobuchi
    • Department of SurgeryMemorial Sloan-Kettering Cancer Center
  • José Manuel García-Castellano
    • Department of SurgeryMemorial Sloan-Kettering Cancer Center
  • Shaji Philip
    • Division of Hematology/Oncology, Department of PediatricsThe Children’s Hospital at Montefiore
  • John H. Healey
    • Department of SurgeryMemorial Sloan-Kettering Cancer Center
    • Division of Hematology/Oncology, Department of PediatricsThe Children’s Hospital at Montefiore
Symposium: Molecular Genetics in Sarcoma

DOI: 10.1007/s11999-008-0328-y

Cite this article as:
Mizobuchi, H., García-Castellano, J.M., Philip, S. et al. Clin Orthop Relat Res (2008) 466: 2052. doi:10.1007/s11999-008-0328-y

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.

Copyright information

© The Association of Bone and Joint Surgeons 2008