Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?
OBJECTIVE
Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study 59 paediatric pilocytic astrocytomas were compared with 62 adult glioblastomas, as a prototype of tumour angiogenesis.


METHODS
Microvessel density, vessel maturity in terms of basement membrane and pericyte coverage, and turnover of both endothelial and tumour cells, and vascular endothelial growth factor (VEGF) expression were evaluated in tumour tissue, immunohistochemically stained with, respectively, CD34, collagen IV, smooth muscle actin, Ki67/CD34, caspase-3/CD34 and VEGF(-A-D). As an indicator for vessel stability the angiopoietin (ANGPT)-1/ANGPT-2 balance was calculated using Real Time RT-PCR.


RESULTS
Pilocytic astrocytoma and glioblastoma showed similar fractions of vessels covered with basement membrane and pericytes. Overlapping ANGPT-1/ANGPT-2 balance and VEGF-A expression were found. Pilocytic astrocytoma had fewer but wider vessels compared with glioblastoma. Turnover of endothelial and tumour cells were relatively lower in pilocytic astrocytoma. Within pilocytic astrocytoma, higher ANGPT-1/ANGPT-2 balance was correlated with fewer apoptotic endothelial cells. Lower numbers of vessels were correlated with higher VEGF-A expression.


CONCLUSIONS
Despite the fact that pilocytic astrocytoma showed a different vessel architecture compared with glioblastoma, a critical overlap in vessel immaturity/instability and the angiogenic profile was seen between both tumours. These findings suggest encouraging possibilities for targeting angiogenesis (for instance with anti-VEGF) as a therapeutic strategy in pilocytic astrocytoma.
Sie
M
M
Department of Pediatrics, Beatrix Children's Hospital, Pediatric Oncology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
de Bont
E S J M
ES
Scherpen
F J G
FJ
Hoving
E W
EW
den Dunnen
W F A
WF
D000293:Adolescent; D042501:Angiogenic Proteins / Q000378:metabolism; D042683:Angiopoietin-1 / Q000096:biosynthesis; D042702:Angiopoietin-2 / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D002196:Capillaries / Q000473:pathology; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D005909:Glioblastoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D012039:Regional Blood Flow; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A