Angiogenesis is a key feature during
oncogenesis and remains a potential target of antiangiogenic
therapy. While commonly described in high-grade lesions, vascularization and its correlation with prognosis in grade I
meningiomas is largely unexplored. In the histological classification, not only the number but also the composition of blood vessels seems to be important. Therefore,
tumor vessel density and
fibrosis were correlated with clinical and imaging variables and prognosis in 295 patients with intracranial grade I
meningioma. Expression of pro-
angiogenic proteins within the
meningiomas was investigated by
proteome analyses and further validated by immunohistochemical staining. Fibrotic
tumor vessels (FTV) were detected in 48% of all
tumors and strongly correlated with vessel density, but not with the histopathological
tumor subtype. Occurrence of FTV was correlated with a 2-fold increased risk of recurrence in both univariate and multivariate analyses. Explorative
proteome analyses revealed upregulation of
VEGF (
vascular endothelial growth factor), PlGF (placental
growth factor), and
IGFBP-3 (insulin-like growth factor-binding protein-3) in
tumors displaying FTV. Immunohistochemical analyses confirmed strong correlations between
tumor vessel
fibrosis and expression of
VEGF, PlGF, and
IGFBP-3. Presence of FTV was strongly associated with disruption of the arachnoid layer on preoperative MRI in univariate and multivariate analyses. In summary, the occurrence of fibrotic
tumor vessels in grade I
meningiomas is strongly associated with vessel density, disruption of the arachnoid layer, expression of
VEGF, PlGF,
IGFBP-3 and
tumor recurrence.