Hypoxia markers in human osteosarcoma: An exploratory study

Hiroo Mizobuchi, José Manuel García-Castellano, Shaji Philip, John H. Healey, Richard Gorlick

Research output: Contribution to journalArticle

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2052-2059
Number of pages8
JournalClinical orthopaedics and related research
Volume466
Issue number9
DOIs
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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    Mizobuchi, H., García-Castellano, J. M., Philip, S., Healey, J. H., & Gorlick, R. (2008). Hypoxia markers in human osteosarcoma: An exploratory study. Clinical orthopaedics and related research, 466(9), 2052-2059. https://doi.org/10.1007/s11999-008-0328-y