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Neuro Oncol. 2016 Feb;18(2):173-83. doi: 10.1093/neuonc/nov288. Epub 2015 Nov 30.

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.

Author information

1
Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany (P.B., A.-E.B., M.D., P.Z., K.H., L.M., K.H.P., P.N.H., M.Mi.); Department of Neurosurgery, Goethe University, Frankfurt, Germany (K.F., V.S.); Dr. Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Frankfurt am Main, Germany (K.F., O.B., J.P.S.); Department of Neuroradiology, University of Frankfurt am Main, Frankfurt am Main, Germany (E.H.); Department of Neurosurgery, University Hospital, Freiburg, Germany (M.Ma.); Cancer Consortium (DKTK), Heidelberg, Germany (O.B., J.P.S., K.H.P, P.N.H., M.Mi.); German Cancer Research Center (DKFZ), Heidelberg, Germany (O.B., J.P.S., K.H.P., P.N.H., M.Mi.); Department of Pathology, University of Heidelberg, Heidelberg, Germany (B.G.).

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.

KEYWORDS:

VEGF; VEGF receptors; antiangiogenic therapy; bevacizumab; glioma

PMID:
26627848
PMCID:
PMC4724185
DOI:
10.1093/neuonc/nov288
[Indexed for MEDLINE]
Free PMC Article

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