Although the role of angiogenesis in
tumor progression and response to treatment is generally well-characterized, for
neuroblastomas clinical data regarding the contribution of angiogenesis and its predictive capacity remain unclear. The aim of this study was to evaluate whether
tumor vascularity in the combination with expression of
vascular endothelial growth factor (
VEGF) represent prognostic factors for patients with
neuroblastoma. Immunohistochemistry using anti-CD34 and anti-
VEGF antibodies was used to analyze
paraffin-embedded primary
tumor tissues from 56 patients diagnosed with
neuroblastoma.
Tumor vascularity was estimated by calculating the
tumor vascular volume fraction (TVVF), and
VEGF expression was determined using semi-quantitative scoring. Statistical analyses including multivariate analysis were performed and compared with these two factors.
Tumor vascularity had impact on survival of high
VEGF expression
neuroblastoma patients. Combination of high
VEGF expression and TVVF value < or = 5% was independent predictor of overall survival (p-value = 0.0041, odds ratio (OR) (95% CI) = 8.67 (1.99-37.69) by the Cox proportional hazards model). This study revealed for the first time a group of extremely high-risk
neuroblastoma with both high
VEGF expression and poor vascularity. For these patients reduced rates of survival were observed (37% vs. 92.5%) (p < 0.0001). These patients did not experience a significant improvement following
hematopoietic stem cell transplantation, and could be candidates for receiving novel
therapies. These results indicate the importance of the mutual relationship between
tumor vascularity and
VEGF, because it gives better insight into the prognosis of patients with
neuroblastoma.