Abstract 15

The prognostic value of microvessel density and angiogenic factor expression in human osteosarcoma

Eugene T. Ek, Yasuyuki Kitagawa, Peter F.M. Choong, Joseline Ojaimi

Department of Orthopaedics, University of Melbourne, St. Vincent's Hospital, Melbourne, Australia

Despite recent advancements in neoadjuvant and adjuvant chemotherapy for osteosarcoma, 25-50% of patients, without evidence of systemic disease at initial diagnosis, subsequently develop metastatic disease, and this remains the major cause of death from this tumour. Several factors that have been identified as independent prognostic markers in osteosarcoma, however the role of angiogenesis still remains a topic of debate. This study aims to evaluate the significance of the degree of angiogenesis and expression of angiogenesis-related genes in osteosarcoma and correlate it with long-term clinical outcome. Archival pre-chemotherapy biopsy tissue of 25 patients with osteosarcoma that were treated at St. Vincent's Hospital, Melbourne was reviewed and the tissue was processed for immunohistochemical identification of microvascular endothelial cells with antibodies directed against CD31 and CD34. Assessment was made of the degree of angiogenesis, as determined by the microvessel density (MVD), and further histological examination was performed looking at the immunohistochemical expression pattern of VEGF (proangiogenic factor) and PEDF (anti-angiogenic factor). This was then correlated with patient outcome, in terms of recurrence, metastasis and death. We hypothesise that increased vascularity in osteosarcoma is associated with increased risk of metastasis and poor prognosis and that potential molecular defects in key endogenous antiangiogenic factors normally expressed in osteoblasts are likely to be responsible for the increased angiogenesis seen in osteosarcoma.

Abbreviations: PEDF - pigment epithelium derived factor; VEGF - vascular endothelium growth factor

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