Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study

Pistolesi, Sabina; Boldrini, Laura; Gisfredi, Silvia; Ieso, Katia De; Camacci, Tiziano; Caniglia, Michele; Lupi, Giancarlo; Leocata, P; Basolo, Fulvio; Pingitore, Raffaele; Parenti, G; Fontanini, Gabriella

doi:10.1046/j.0305-1846.2003.00516.x

Cited by 80 publications

(84 citation statements)

References 25 publications

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“…The elevated levels of VEGF seen in this study confirm earlier reports not only on benign meningiomas, but atypical and malignant ones as well (40). It has been suggested that the increased ratio of the pro-angiogenesis factor VEGF to the anti-angiogenic factor SEMASA (which is expressed in human meningiomas association with low microvessel density) is a negative predictor of recurrence in these neoplasms (41).…”

Section: Discussionsupporting

confidence: 80%

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai

Martin

King

et al. 2016

International Journal of Oncology

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Abstract. MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

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Section: Discussionsupporting

confidence: 80%

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Rooprai

Martin

King

et al. 2016

International Journal of Oncology

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“…43 As our working group could demonstrate in a previous study including 17 dogs, its expression is a predictive factor for survival in dogs with intracranial meningiomas. 38 The current study confirmed in a large number of samples that VEGF is expressed in intracranial meningioma tissue from dogs, with positive labeling in 67/70 (96%) of the tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Our study did not reveal any association of VEGF and Ki-67 expression in intracranial meningioma in dogs, despite evidence that increased vascularization is associated with higher proliferation in human meningiomas. 43,44 It is interesting that even in the outlier that revealed an extraordinary high MIB-LI of 43.1, only 25-50% of cells stained positive for VEGF, and staining intensity was considered as mild. Upregulation of VEGF induced by hypoxia in the most central or necrotic components of the tumor 55 might have influenced results in our study as we did not control for the presence or absence of necrosis and no information was available on where within the tumor the sample was collected.…”

Section: Discussionmentioning

confidence: 99%

“…38 Solid tumors are dependent on angiogenesis for growth beyond 2 mm in diameter, 41,42 and correlation of meningioma vascularity expressed as microvascular density and MIB-1 LI has been documented in humans. 43 In addition, an association of strong angiogenic recruitment and increased VEGF expression with rapid tumor growth indicated by Ki-67 expression has been suggested. 44 The knowledge of mechanisms that are responsible for progression of tumor disease is prerequisite for developing future therapeutic strategies and little is known about the biological behavior of intracranial meningioma in dogs.…”

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confidence: 99%

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Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

Matiasek¹,

Platt²,

Adams³

et al. 2009

Veterinary Internal Medicne

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Background: Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas.Hypothesis: Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome.Animals: Seventy client-owned dogs with WHO grade I intracranial meningiomas. Methods: Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fisher's exact tests and nonparametric Spearman's rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures.Results: Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival.Conclusions and Clinical Importance: MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.

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“…Vascular endothelial growth factor (VEGF) and its receptors are reported to play a major role in angiogenesis, vascular permeability, and tumor recurrence in human meningiomas. 49,50 Both VEGF and its major receptor VEGFR-2 are upregulated in canine meningiomas. 6,8 Survival time for canine meningioma patients was inversely associated with VEGF expression in 1 series, 8 although all tumors were benign (Grade I).…”

mentioning

confidence: 99%

Magnetic Resonance Imaging and Histological Classification of Intracranial Meningiomas in 112 Dogs

Sturges¹,

Dickinson²,

Bollen³

et al. 2008

Veterinary Internal Medicne

153

272

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Background: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated.Hypothesis: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics.Animals: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. Methods: Retrospective observational study.Results: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P o .05) associations were found among tumor subtype or grade and any of the MRI features studied.Conclusions and Clinical Importance: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.

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Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study

Cited by 80 publications

References 25 publications

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma

Ki‐67 and Vascular Endothelial Growth Factor Expression in Intracranial Meningiomas in Dogs

Magnetic Resonance Imaging and Histological Classification of Intracranial Meningiomas in 112 Dogs

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