Original scientific paper
Relationship Between Tumor Vascularity and Vascular Endothelial Growth Factor as Prognostic Factors for Patients with Neuroblastoma
Gordana Jakovljević
Srđana Čulić
Jasminka Stepan
Iva Košuta
Sven Seiwerth
Abstract
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 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.
Keywords
neuroblastoma; tumor angiogenesis; vascular endothelial growth factor; hypoxia; survival
Hrčak ID:
75610
URI
Publication date:
30.12.2011.
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