10005-ANGI-1 REGULATION OF ALTERNATIVE ANGIOGENIC FACTORS IN BEVACIZUMAB THERAPY FOR GLIOBLASTOMA

Abstract The elucidation of the mechanism of action and resistance is imperative to overcome resistance to Bev and develop a more effective therapy. This study aims to investigate the status and change of alternative angiogenic factors regarding Bev usage using human specimens. The present study used 54 glioblastoma tissues obtained at 3 different settings: tumors of initial resection (naive Bev group), tumors resected following Bev therapy (effective Bev group), and recurrent tumors after Bev therapy (refractory/autopsied Bev group). Importantly, naive Bev-refractory Bev of 22 specimens in 11 cases (including 4 autopsy specimens and 7 salvage surgery specimens) were obtained as paired specimens from the same patient. The expression of alternative angiogenic factors including basic fibroblast growth factor (bFGF), placental growth factor (PlGF), Angiopoietin1 (Ang-1), Angiopoietin2(Ang-2) and EphrinA2 were investigated via immunohistochemistry. PlGF expression was higher in the effective group than in the Naive group (p=0.048), and Ang-2 (0.047) and EphA2 (p=0.028) were higher in the relapse group than in the Naive group. Interestingly, in paired specimens, PlGF expression was higher in the refractory group than in the Naive group (p=0.036). This suggests that angiogenic factors other than VEGF are involved in recurrence. We provide the first clinicopathological evidence of the status of alternative angiogenic pathway after the Bev usage. These in situ observations will help to optimize therapy.