Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients
Open Access
- 2 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Molecular Histology
- Vol. 52 (2), 233-243
- https://doi.org/10.1007/s10735-020-09940-2
Abstract
Higher grade meningiomas tend to recur. We aimed to evaluate protein levels of vascular endothelial growth factor (VEGF)-A with the VEGF-receptors 1-3 and the co-receptors Neuropilin (NRP)-1 and -2 in WHO grade II and III meningiomas to elucidate the rationale for targeted treatments. We investigated 232 specimens of 147 patients suffering from cranial meningioma, including recurrent tumors. Immunohistochemistry for VEGF-A, VEGFR-1-3, and NRP-1/-2 was performed on tissue micro arrays. We applied a semiquantitative score (staining intensity x frequency). VEGF-A, VEGFR-1-3, and NRP-1 were heterogeneously expressed. NRP-2 was mainly absent. We demonstrated a significant increase of VEGF-A levels on tumor cells in WHO grade III meningiomas (p = 0.0098). We found a positive correlation between expression levels of VEGF-A and VEGFR-1 on tumor cells and vessels (p < 0.0001). In addition, there was a positive correlation of VEGF-A and VEGFR-3 expression on tumor vessels (p = 0.0034). VEGFR-2 expression was positively associated with progression-free survival (p = 0.0340). VEGF-A on tumor cells was negatively correlated with overall survival (p = 0.0084). The VEGF-A-driven system of tumor angiogenesis might still present a suitable target for adjuvant therapy in malignant meningioma disease. However, its role in malignant tumor progression may not be as crucial as expected. The value of comprehensive testing of the ligand and all receptors prior to administration of anti-angiogenic therapy needs to be evaluated in clinical trials.Keywords
Funding Information
- Projekt DEAL
This publication has 29 references indexed in Scilit:
- Microvascularization and expression of VEGF and its receptors in recurring meningiomas: pathobiological data in favor of anti-angiogenic therapy approachesClinical Neuropathology, 2012
- Bevacizumab therapy for adults with recurrent/progressive meningioma: a retrospective seriesJournal of Neuro-Oncology, 2012
- Hypoxia differentially regulates VEGFR1 and VEGFR2 levels and alters intracellular signaling and cell migration in endothelial cellsBiochemical and Biophysical Research Communications, 2011
- Observer variation in immunohistochemical analysis of protein expression, time for a change?Histopathology, 2006
- A peptide competing with VEGF165 binding on neuropilin-1 mediates targeting of a chlorin-type photosensitizer and potentiates its photodynamic activity in human endothelial cellsJournal of Controlled Release, 2006
- Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesisExperimental Cell Research, 2006
- Differential Transcriptional Regulation of the Two Vascular Endothelial Growth Factor Receptor GenesOnline Journal of Public Health Informatics, 1997
- Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesisNature, 1992
- Defect-induced melting and solid-state amorphizationNature, 1992
- Multiple microsample analysis of intratumor estrogen receptor distribution in breast cancers by a combined biochemical/immunohistochemical methodEuropean Journal of Cancer and Clinical Oncology, 1987