Differences in vasculature between pilocytic and anaplastic astrocytomas of childhood.
BACKGROUND
The clinical manifestations of childhood pilocytic astrocytoma (PA) and anaplastic astrocytoma (AA) markedly differ, especially in the time to progression and prognosis. Because of the aggressive course and poor survival rate of AA, one would expect it to be associated with a high angiogenic index. Counterintuitively, we often find higher microvessel density counts in PA than in AA.


METHODS
We examined the differences in type or density of microvasculature between the two neoplasms. To differentiate established, mature vessels from immature growing ones, we used antibodies to Factor VIII (FVIII) to stain endothelial cells (ECs) of blood vessels and alpha-smooth muscle actin (alpha-SMA) antibodies to stain vessels supported by adventitia.


RESULTS
We found that large, mature, alpha-SMA-positive vessels predominated in PA, and small, immature, alpha-SMA-negative vessels in AA. The vessel maturation index was 54.5% for PA, and 6.1% for AA. Immunostaining with vascular endothelial growth factor (VEGF) and anti-flt-1/VEGF receptor-1 antibodies showed distinct tissue patterns. VEGF immunoreactivity occurred mainly in the processes of the tumor astrocytes in PA; the opposite was observed in AA. flt-1/VEGFR-1 was detected in the tumor cells of AA but not in those of PA.


CONCLUSIONS
We propose that the predominance of small, alpha-SMA-negative vessels in AA represents immature, unstable vasculature with a potentially greater susceptibility to anti-angiogenic therapy. The expression of both flt-1 and VEGF by AA tumor cells also suggests a possible autocrine growth-promoting function for VEGF in addition to its role as paracrine pro-angiogenic growth factor for activated ECs, thus making anti-angiogenesis an attractive therapeutic target in the treatment of AA.
Department of Paediatrics, New Agent and Innovative Therapy Program, Toronto, Ontario, Canada.
Benjamin
B
Gesundheit
Giannoula
G
Klement
Christof
C
Senger
Robert
R
Kerbel
Mark
M
Kieran
Sylvain
S
Baruchel
Laurence
L
Becker
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001254:Astrocytoma / Q000098:blood supply* / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D040281:Vascular Endothelial Growth Factor Receptor-1
D020533:Angiogenesis Inhibitors; D016326:Extracellular Matrix Proteins; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1