gms | German Medical Science

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.