Abstract 1381: Overlapping high pro- and anti-angiogenic VEGF-A isoform ratio between pediatric pilocytic astrocytoma and adult glioblastoma suggests possibilities for anti-angiogenic therapy in pilocytic astrocytoma
Authors: Sie Mariska , den Dunnen Wilfred F.A. , Scherpen Frank J.G. , Hoving Eelco W. , de Bont Eveline S.J.M. 
Published: August 2012

Abstract
Introduction. Pilocytic astrocytoma (WHO grade I), the most frequent brain tumor in children, showed a critical overlap with the angiogenic profile and vessel immaturity/instability of glioblastoma (WHO grade IV). However, the highly vascular pilocytic astrocytoma had fewer but wider vessels compared with glioblastoma,(Sie et al. NAN 2010) possibly due to different VEGF-A isoform expression. So this study aimed to analyze VEGF-A isoforms in correlation with tumor vasculature in pilocytic astrocytoma and glioblastoma. As it is hypothesized that tumors with relatively higher pro- (VEGF-AXXXa) than anti-angiogenic (VEGF-AXXXb) isoform expression will be more sensitive to anti-angiogenic therapy, because VEGF-AXXXb inhibits the effect of anti-VEGF-A antibodies like bevacizumab, we secondly aimed to determine the VEGF-AXXXa: VEGF-AXXXb ratio. Materials and methods. VEGF-A isoforms were analyzed in tumor tissue of 15 pediatric pilocytic astrocytoma and 12 adult glioblastoma patients using Real Time RT-PCR. Microvessel density, vessel maturity in terms of basement membrane and pericyte coverage, and endothelial and tumor cell turnover were evaluated in immunohistochemically stained slides with CD34, collagen IV, smooth muscle actin, Ki67/CD34 and caspase-3/CD34 respectively. The angiopoietin-1/-2 balance as indicator for vessel stability was assessed using Real Time RT-PCR. Results. All pro-angiogenic VEGF-A isoforms (VEGF-A121a, 145, 148, 165, 183, 189) were lower expressed in pilocytic astrocytoma compared with glioblastoma. However, analyzing these isoforms relative to VEGF-A121a as it is expressed by normal cells, no significant differences were found between both tumors. Pilocytic astrocytoma showed an association between VEGF-A165a and their dilatated vessels, while VEGF-A189a was associated with the characteristic small blood vessels in glioblastoma. In both tumors, VEGF-A189a was correlated with less vessel immaturity (r: 0.621, P = 0.024; r: 0.697, P = 0.025). Surprisingly, pilocytic astrocytoma and glioblastoma showed an overlapping VEGF-AXXXa: VEGF-AXXXb ratio with relatively higher VEGF-A165a and VEGF-A189a expression (P = 0.486; P = 0.456). Conclusion(s). This study showed that VEGF-A isoforms were associated with the different vessel architecture in pilocytic astrocytoma and glioblastoma. Interestingly, a clear overlap was found between both tumors in the VEGF-A isoform ratios with relatively high VEGF-A165a and VEGF-A189a expression. These findings suggest encouraging possibilities for anti-angiogenic therapy, for instance with bevacizumab, in pilocytic astrocytoma, especially for those children with unresectable tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1381. doi:1538-7445.AM2012-1381