Differential expression of vascular endothelial growth factor A, its receptors VEGFR-1,-2, and-3 and co-receptors neuropilin-1 and-2 does not predict bevacizumab response in human astrocytomas

Peter Baumgarten, Anna Eva Blank, Kea Franz, Elke Hattingen, Maika Dunst, Pia Zeiner, Katharina Hoffmann, Oliver Bähr, Lisa Mäder, Benjamin Goeppert, Marcia MacHein, Volker Seifert, Joachim P. Steinbach, Karl H. Plate, Patrick N. Harter, Michel Mittelbronn*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

Abstract

Background A major hallmark of malignant progression in human astrocytomas is the formation of new blood vessels. Antiangiogenic therapy using the anti-vascular endothelial growth factor (VEGF)-antibody bevacizumab leads to increased progression-free survival in glioblastoma patients but does not influence their overall survival. To date, it is unclear why antiangiogenic therapy fails in many glioblastoma patients, while a small subpopulation profits considerably from this treatment. Methods The aim of our study was to determine the expression of VEGF-A and its (co-) receptors by immunohistochemistry and to test the association with patient survival in 350 glioma patients. Additionally, VEGF-A expression was analyzed by in-situ hybridization. In 18 patients, the protein expression was compared with the bevacizumab response according to extended and modified RANO criteria. Results We found a heterogeneous expression pattern of VEGF and its receptors in glioblastoma patients with significantly lower levels in WHO grade II and III tumors and normal-appearing brain tissue (P <. 001). Pilocytic astrocytomas (WHO grade I) showed significantly higher VEGFR-1,-2 and neuropilin-1 levels as compared to WHO grade II and III astrocytomas (P <. 01) but at lower levels than glioblastomas. The expression of neuropilin-2 was low in all tumors. There was neither a significant correlation between protein expression and patient survival nor between protein levels and bevacizumab response after modified RANO criteria. Conclusion Since our data indicate that beneficial response to bevacizumab treatment is independent of the expression of VEGF-A and its (co-) receptors, further investigation is needed to decipher the underlying mechanisms of antiangiogenic treatment response.

Original languageEnglish
Pages (from-to)173-183
Number of pages11
JournalNeuro-Oncology
Volume18
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

Keywords

  • VEGF
  • VEGF receptors
  • antiangiogenic therapy
  • bevacizumab
  • glioma

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