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Hypoxia Markers in Human Osteosarcoma: An Exploratory Study

  • Symposium: Molecular Genetics in Sarcoma
  • Published:
Clinical Orthopaedics and Related Research

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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Acknowledgments

We thank the late Andrew Huvos, MD, Department of Pathology, and Alexander Chou, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, for their contributions to this study.

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Hiroo Mizobuchi MD, José Manuel García-Castellano MD, PhD & John H. Healey MD

  2. Division of Hematology/Oncology, Department of Pediatrics, The Children’s Hospital at Montefiore, 3415 Bainbridge Avenue, Rosenthal 3rd Floor, Bronx, NY, 10467, USA

    Shaji Philip BA & Richard Gorlick MD

Authors
  1. Hiroo Mizobuchi MD
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  2. José Manuel García-Castellano MD, PhD
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  3. Shaji Philip BA
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  4. John H. Healey MD
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  5. Richard Gorlick MD
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Corresponding author

Correspondence to Richard Gorlick MD.

Additional information

One or more of the authors (RG) have received funding from the National Cancer Institute (Grant Number R01 CA 83132) and the Yurman Limb Preservation Fund.

Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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Mizobuchi, H., García-Castellano, J.M., Philip, S. et al. Hypoxia Markers in Human Osteosarcoma: An Exploratory Study. Clin Orthop Relat Res 466, 2052–2059 (2008). https://doi.org/10.1007/s11999-008-0328-y

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