Fig. 5.

Comparison of effects of anti-VEGF treatment between human and animal specimens. (A) In the tissue from case 3, single endothelial cell wall vasculature was clearly highlighted after staining for factor VIII (×5 magnification). (B–D) The U87 orthotopic xenograft model demonstrated striking changes after bevacizumab treatment. (B) Hematoxylin and eosin staining (×2.5 magnification) demonstrated typical (control) growth of U87 cells in the mouse brain, with a sharply defined leading edge of the tumor (white arrows). (C) In contrast, in animals treated with bevacizumab, tumor growth was infiltrative in nature (×2.5 magnification). Factor VIII staining highlighted the robust clusters of vessels in the infiltrating tumor. (D) A higher magnification (×10) of this infiltrating leading edge of the mouse xenograft tumor. Particularly important are the extension and infiltration of tumor cells beyond the dense vasculature (white arrows). The perivascular invasion noted in C and D contrasted with the more infiltrative growth pattern seen in the human tumor samples. CA9 staining in human (E) and U87 xenograft (F) tumor tissue. Prolonged, continuous antiangiogenic treatment significantly increased CA9 staining in tumor. Note the areas of necrosis and hypoxia adjacent to single endothelial cell vasculature (black arrows) and the dilated vessel with surrounding fibrosis.