420P - Impact of tumor microenvironment on the expression of vascular endothelial growth factor receptor 2 in glioblastoma multiforme

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Central Nervous System Malignancies
Pathology/Molecular Biology
Translational Research
Presenter Mikk Saretok
Citation Annals of Oncology (2014) 25 (suppl_4): iv137-iv145. 10.1093/annonc/mdu330
Authors M. Saretok1, A. Adamson2, T. Jogi3, M. Joonsalu4, M. Kase5, A. Minajeva6, J. Lukjanova2, T. Metsaots2, M. Vardja3, T. Asser7, J. Jaal8
  • 1Dept Of Radiotherapy And Oncological Therapy, Tartu University Hospital, Haematology and Oncology Clinic, 51014 - Tartu/EE
  • 2Faculty Of Medicine, University of Tartu, 51014 - Tartu/EE
  • 3Dept Of Radiotherapy And Oncological Therapy, Tartu University Hospital, Haematology and Oncology Clinic, Tartu/EE
  • 4Hematology And Oncology, Tartu University Clinics, 51014 - Tartu/EE
  • 5Center Of Oncology, East Tallinn Central Hospital, Tallinn/EE
  • 6Faculty Of Medicine, University of Tartu, Tartu/EE
  • 7Dept Of Neurosurgery, Tartu University Hospital, Tartu/EE
  • 8Dept Of Radiotherapy And Oncological Therapy, Tartu University Hospital, 51003 - Tartu/EE

Abstract

Aim

The aim of our study was to evaluate the impact of tumor microenvironment (visual inflammation, inflammatory ICAM-1 expression) on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2).

Methods

Surgically excised GBM tissues (n = 42) were histologically examined for the overall extent of inflammation (score 1-3, based on typical appearance of inflammation, including presence of edema and inflammatory cell infiltration). After immunohistochemical staining procedure, tissue expression of ICAM-1 (optical density using pixel analysis software) as well as the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field) and endothelial staining intensity of VEGFR-2 (score 0-3) were determined.

Results

In individual GBM samples, the extent of inflammation varied, being in the whole group 1.9 ± 0.7 (mean ± SD). Mean optical density of ICAM-1 (one of the mediators of inflammation) was 57,0 ± 27.1 (mean ± SD). The number of VEGFR-2+ blood vessels per microscopic field and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 (mean ± SD) and 1.2 ± 0.8 (mean ± SD) respectively. A positive association was found between VEGFR-2 staining intensity and the extent of inflammation (p = 0.005). Moreover, VEGFR-2 staining intensity correlated with the expression level of tissue ICAM-1 (p = 0.026).

Conclusions

The expression of VEGFR-2 – one of the targets of anti-angiogenic therapy – depends on GBM microenvironment. Importantly, higher VEGFR-2 levels were seen in the presence of more pronounced inflammation, whereas in less inflamed tissues only weak expression of VEGFR-2 was found. Later has to be taken into consideration when VEGFR-2 targeting anti-angiogenetic drugs are tested in the treatment of GBM. This work was supported by grant IUT2-4.

Disclosure

All authors have declared no conflicts of interest.