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No data exist on angiogenic patterns and their prognostic impact in human glioblastoma. Such data are relevant for translation of antiangiogenic therapies into clinical applications. Using immunohistochemistry for CD34, we assessed vascular patterns in 114 primary glioblastomas. Vascular patterns comprised unevenly distributed glomeruloid/garland-like/clustered bizarre vascular formations and evenly distributed delicate capillary-like microvessels ("classic" vascular pattern). The combination of low content of bizarre vascular formations and prominent classic vascular pattern (n=29) was an independent factor for longer survival (p=0.006, Cox regression), as well as postoperative high Karnofsky performance status (p=0.005). In patients with a prominent classic vascular pattern, there was no difference of MIB1 labeling index whereas microvessel density and apoptotic index (TUNEL) were significantly higher as compared to all other patients (p<0.05). In addition, diffuse expression of hypoxia-inducible factor (HIF)-1alpha and strong expression of vascular endothelial growth factor were more common (p<0.05, Chi-square test). FISH revealed loss of chromosomes 1p and 19q only in 1/7 long-time survivors with classic pattern. We conclude that vascular patterns in primary glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins. Our findings denote for the first time distinct angiogenic subtypes of human glioblastoma which may prove relevant for anti-angiogenic therapy approaches.

Type

Journal article

Journal

Brain pathol

Publication Date

04/2003

Volume

13

Pages

133 - 143

Keywords

Adult, Aged, Antigens, CD34, Brain Neoplasms, Endothelial Growth Factors, Glioblastoma, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, In Situ Nick-End Labeling, Intercellular Signaling Peptides and Proteins, Ki-67 Antigen, Lymphokines, Middle Aged, Neovascularization, Pathologic, Survival Analysis, Tissue Distribution, Transcription Factors, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors