Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma.
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.
Kaya
M
M
Divison of Orthopedic Surgery and Department of Clinical Research, National Sapporo Hospital, Kikusui 4-2, Shiroishi-ku, Sapporo, 003-0804 Hokkaido, Japan. kaya@sap-cc.go.jp
Wada
T
T
Kawaguchi
S
S
Nagoya
S
S
Yamashita
T
T
Abe
Y
Y
Hiraga
H
H
Isu
K
K
Shindoh
M
M
Higashino
F
F
Okada
F
F
Tada
M
M
Yamawaki
S
S
Ishii
S
S
D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000097:blood* / Q000098:blood supply / Q000473:pathology; D016228:Endothelial Growth Factors / Q000032:analysis / Q000097:blood*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008222:Lymphokines / Q000032:analysis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000097:blood* / Q000098:blood supply / Q000473:pathology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor