TY - JOUR
T1 - Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?
AU - Sie, M
AU - de Bont, E S J M
AU - Scherpen, F J G
AU - Hoving, E W
AU - den Dunnen, W F A
N1 - © 2010 The Authors. Neuropathology and Applied Neurobiology © 2010 British Neuropathological Society.
PY - 2010/12
Y1 - 2010/12
N2 - AIMS: 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.
AB - AIMS: 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.
KW - Adolescent
KW - Angiogenic Proteins/metabolism
KW - Angiopoietin-1/biosynthesis
KW - Angiopoietin-2/biosynthesis
KW - Brain Neoplasms/blood supply
KW - Capillaries/pathology
KW - Cell Proliferation
KW - Child
KW - Child, Preschool
KW - Endothelial Cells/physiology
KW - Female
KW - Glioblastoma/blood supply
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Male
KW - Neovascularization, Pathologic/genetics
KW - Regional Blood Flow
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Vascular Endothelial Growth Factor A/biosynthesis
U2 - 10.1111/j.1365-2990.2010.01113.x
DO - 10.1111/j.1365-2990.2010.01113.x
M3 - Article
C2 - 20704656
SN - 0305-1846
VL - 36
SP - 636
EP - 647
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
IS - 7
ER -