1. ¹Divison of Orthopedic Surgery and Department of Clinical Research, National Sapporo Hospital, Kikusui 4-2, Shiroishi-ku, Sapporo, 003-0804, Hokkaido, Japan
2. ²Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Hokkaido, Japan
3. ³Department of Oral Pathobiology, Hokkaido University Graduate School of Dental Medicine, N-13, W-7, Kita-ku, Sapporo 060-8586, Hokkaido, Japan
4. ⁴Division of Cancer Pathobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-0815, Hokkaido, Japan
5. ⁵Division of Cancer-Related Genes, Research Section of Molecular Pathogenesis, Institute for Genetic Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-0815, Hokkaido, Japan

Correspondence: M Kaya, E-mail: kaya@sap-cc.go.jp

Received 23 August 2001; Revised 31 December 2001; Accepted 22 January 2002.

Abstract

To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann–Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma.