gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Neuropathological and molecular features of recurrent glioblastomas following antiangiogenic treatment with bevacizumab

Meeting Abstract

  • Jörg Felsberg - Institut für Neuropathologie, Heinrich Heine Universität Düsseldorf, Düsseldorf, Deutschland
  • Ghazaleh Tabatabai - Klinik für Neurologie, Universitätsspital Zürich, Zürich, Schweiz
  • Michael Sabel - Klinik für Neurochirurgie, Heinrich Heine Universität Düsseldorf, Düsseldorf, Deutschland
  • Silvia Hofer - Klinik für Onkologie, Universitätsspital Zürich, Zürich, Schweiz
  • Manfred Westphal - Klinik für Neurochirurgie, Universitätsklinik Hamburg, Hamburg, Deutschland
  • Guido Reifenberger - Institut für Neurochirurgie, Heinrich Heine Universität, Düsseldorf

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocP 097

doi: 10.3205/13dgnc514, urn:nbn:de:0183-13dgnc5145

Published: May 21, 2013

© 2013 Felsberg et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Objective: Bevacizumab (BEV) is a monoclonal antibody to vascular endothelial growth factor that has been approved for the treatment of patients with recurrent glioblastoma. We aimed to characterize neuropathological and molecular features in recurrent malignant gliomas after failure of BEV treatment.

Method: We investigated tissue samples obtained before and after BEV treatment from 12 patients with high-grade astrocytomas (10 glioblastomas, 2 anaplastic astrocytomas). Various histological features, including vessel density, cellularity and proliferative activity, were determined for each tissue sample. In addition, immunohistochemical studies were performed for selected signaling molecules, including phosphoAkt (pAkt), phosphoS6K (pS6K), and cMET. As a control cohort, primary and recurrent tumors from 14 patients with high-grade astrocytomas (13 glioblastomas, 1 anaplastic astrocytoma) without BEV treatment were studied. The respective clinical records and neuroimaging findings were retrospectively reviewed for each patient.

Results: Radiographic recurrence occurred most often at the initial tumor site in both patient groups. Histologically, most recurrences after BEV showed reduced vessel density and less prominent microvascular proliferation in comparison to the corresponding primary tumors. pAkt and pS6K immunoreactivity increased in subsets of recurrences in both patient groups. cMET immunoreactivity was found to be strongly up-regulated in 5/10 patients following BEV treatment.

Conclusions: Our findings confirm that recurrent malignant gliomas following BEV treatment often demonstrate vascular normalization and upregulation of cMET. The combination of BEV and cMET-inhibiting strategies may therefore be considered as an interesting approach to delay or overcome BEV failure in glioblastoma.