Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma

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.

Figure 1

Relationship between microvessel count and serum angiogenic factors levels. Serum angiogenic factors levels against the vessel counts in 16 patients with osteosarcoma. (A) VEGF, (B) VEGF corrected for platelet counts (C) bFGF and (D) PlGF. The microvessel counts of the primary osteosarcoma tumours correlated with serum VEGF level (P=0.004). and serum VEGF/Plt level (P=0.0057). In contrast, no statistically significant correlation was observed between the serum PlGF or serum bFGF level and microvessel density.

Figure 2

Relationship between the disease relapse and serum concentration of each angiogenic factor. The differences in each angiogenic factor level between the no-relapse and relapse group. The serum levels of VEGF and the serum levels of VEGF corrected for the count of platelet were significantly higher in the patients of the relapse group. In contrast, there was no significant differences in the serum PlGF or serum bFGF level between the two groups.

Figure 3

Relationship between the tumour volume or tumour VEGF expression serum VEGF level and disease relapse. (A) Relationship between the serum VEGF level and tumour volume. (B) Relationship between serum concentration of VEGF and in vivo expression of VEGF protein in the primary osteosarcoma tumour. (C) Relationship between the disease relapse and tumour volume.