Quantification of angiogenesis stimulators in children with solid malignancies

Humoral angiogenesis stimulators including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been implicated in the pathogenesis of solid malignancies. However, it has remained unclear whether both stimulators contribute to the development and progression of solid malignancies of children. The aim of the present study was to determine whether VEGF and bFGF are elevated in body fluids of children with solid malignancies and, if so, whether these elevated levels correlate with clinical parameters. Using enzyme-linked immunosorbent assays (ELISAs), we quantified VEGF and bFGF in serum (n = 107) and urine (n = 57) of healthy children and of children with solid malignancies (serum: n(VEGF) = 69, n(bFGF) = 60; urine: n(VEGF) or n(bFGF) = 13). Finally, we compared patients' pre-therapeutic and post-therapeutic levels. Serum VEGF was elevated in children with several solid tumors (Ewing's sarcoma, primitive neuroectodermal tumours, malignant lymphoma, Langerhans cell histiocytosis and medulloblastoma). In contrast, serum bFGF, urinary bFGF or urinary VEGF were not significantly elevated. Upon successful therapy, elevated pre-therapeutic serum VEGF levels declined to levels present in healthy children. VEGF could contribute to the progression of pediatric solid malignancies, and serum VEGF could be used to monitor therapeutic response. Furthermore, the determination of angiogenesis stimulators could identify patients eligible for anti-angiogenic therapy.