Abstract 1306: Tumor vasculature and angiogenic profile of pediatric pilocytic astrocytoma

Abstract

Abstract Introduction: Pilocytic astrocytomas (WHO, grade I astrocytomas) are the most frequent brain tumors in children. Despite a 5-year survival of 90%, outcome is not always favourable, mainly because of surgical morbidity and tumor progression. To reduce this morbidity as well as mortality, new therapeutic modalities are needed. As target in cancer treatment, angiogenesis is extensively investigated, and formed an effective and well tolerated treatment in recurrent adult glioblastomas (WHO, grade IV astrocytomas). However, little is known about angiogenesis in low grade pediatric astrocytomas. So this study aimed to characterize tumor vasculature and the angiogenic profile of 59 pediatric pilocytic astrocytomas to obtain insights into potential angiogenic related therapeutic targets in these tumors. Materials and methods: Microvessel density (MVD), vessel maturity in terms of basement membrane and pericytes coverage, and turnover of both endothelial and tumor cells, and vascular endothelial growth factor (VEGF) expression were evaluated in tumor tissue, immunohistochemically stained with respectively CD34, collagen IV, Smooth Muscle Actin (SMA), Ki67/CD34, caspase-3/CD34, and VEGF(-A-D). Collagen IV and SMA slides were quantified using morphometry software. As indicator for vessel stabilization, the angiopoietin (ANGPT)-1/ANGPT-2 balance was calculated using Real Time RT-PCR. These data were compared with previously described 62 adult glioblastomas,(Sie et al, J Neurosurg 2009) often seen as a model for studying angiogenesis. Results: Pilocytic astrocytoma had fewer but wider vessels than glioblastoma. Slightly thicker pericyte coverage and a higher ANGPT-1/ANGPT-2 balance were seen in pilocytic astrocytoma (respectively p = 0.016, and p = 0.001). Turnover of endothelial and tumor cells were lower in pilocytic astrocytoma (p < 0.001). Within pilocytic astrocytoma, a positive correlation was found between pericytes and basement membrane coverage (r: 0.377, p = 0.005). Higher ANGPT-1/ANGPT-2 balance was correlated with less apoptotic endothelial cells (r: −0.480, p = 0.007). Comparing both tumors, no significant difference was found in basement membrane coverage, the fraction of vessels covered with pericytes, and VEGF-A expression. Proliferating tumor cells were positively correlated with proliferating endothelial cells (r: 0.636, p < 0.001) and VEGF-B expression (r: 0.290, p = 0.029). Conclusion: Despite the fact that pilocytic astrocytomas showed slightly less immature and instable vasculature compared with glioblastoma, a large overlap in the angiogenic profile was seen between both tumors. These findings suggest promising possibilities for targeting angiogenesis with anti-VEGF as therapeutic strategy in pilocytic astrocytoma. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1306.