Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma

Marback, Eduardo Ferrari; Arias, Victor; Paranhos, Augusto; Soares, Fernando Augusto; Murphree, A. Linn; Erwenne, Clélia Maria

doi:10.1136/bjo.87.10.1224

Cited by 52 publications

(32 citation statements)

References 38 publications

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“…9,10 In our study, patients with an advanced stage of disease, indicated by a large tumor volume or the presence of optic nerve invasion, showed a higher degree of AES enhancement, compared with those with early-stage disease. All eyes containing large tumors showed some degree of abnormal AES enhancement, whereas this finding was uncommon in very small and small tumors.…”

Section: Discussionmentioning

confidence: 79%

“…[2][3][4] MR imaging provides the opportunity for a noninvasive evaluation of these risk factors with reasonable diagnostic accuracy. [5][6][7][8] Tumor angiogenesis is also a histopathologic risk factor for local tumor invasion and systemic dissemination in retinoblastoma 9,10 ; initial reports on vascular targeting therapy in mouse models of retinoblastoma show promising results. 11 However, evaluation of angiogenic activity has been performed only in vitro on the histopathology of enucleated eyes.…”

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confidence: 99%

“…The degree of angiogenesis can be assessed by evaluation of angiogenic markers, such as MVD or expression of VEGF and its receptors. 9,10,[12][13][14] High tumor MVD is correlated to invasive growth and metastasis and is associated with poor prognosis. 9,10 VEGF is highly expressed in retinoblastoma, and in addition to promoting angiogenesis, VEGF causes an increased vascular permeability in neovascular capillary beds with subsequent BOB breakdown.…”

mentioning

confidence: 99%

“…9,10,[12][13][14] High tumor MVD is correlated to invasive growth and metastasis and is associated with poor prognosis. 9,10 VEGF is highly expressed in retinoblastoma, and in addition to promoting angiogenesis, VEGF causes an increased vascular permeability in neovascular capillary beds with subsequent BOB breakdown. [12][13][14] Furthermore, released VEGF in the posterior eye segment is able to diffuse into the aqueous of the AC, where it induces IA, spatially separated from the tumor location.…”

mentioning

confidence: 99%

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Contrast-Enhancement of the Anterior Eye Segment in Patients with Retinoblastoma: Correlation between Clinical, MR Imaging, and Histopathologic Findings

Graaf¹,

Valk²,

Moll³

et al. 2009

AJNR Am J Neuroradiol

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Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Contrast-Enhancement of the Anterior Eye Segment in Patients with Retinoblastoma: Correlation between Clinical, MR Imaging, and Histopathologic Findings

Graaf¹,

Valk²,

Moll³

et al. 2009

AJNR Am J Neuroradiol

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“…14,37 Histopathologic studies 38 have also shown that tumor dissemination may be predicted by the number of tumor blood vessels. Moreover, it is well known that pathologic angiogenesis may result in peripheral anterior synechiae and secondary glaucoma, which are both associated with worse retinoblastoma prognosis.…”

Section: Expression Of the Neural Stem Cell Marker Sox2mentioning

confidence: 99%

Expression of Angiogenic Factors in Invasive Retinoblastoma Tumors Is Associated With Increase in Tumor Cells Expressing Stem Cell Marker Sox2

Garcia

Gombos²,

Prospero³

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context Progression of retinoblastoma is associated with increased tumor angiogenesis. However, a clear relationship between the expression of angiogenic markers in specific regions of the tumor and tumor progression has not been established. This study investigates the association between angiogenic factors in retinoblastomas with choroidal and/or optic nerve invasion (high-risk/invasive retinoblastoma) and expression of Sox2, a stem cell marker. Objective To investigate the association between the expression of angiogenic factors and markers of tumor invasiveness, such as the stem cell marker Sox2, in retinoblastoma tissues. Design Immunohistochemistry was used to evaluate coexpression of the angiogenic growth factors vascular endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGFR-2), and endoglin (CD105); markers of glial differentiation (vimentin and glial fibrillary acidic protein); and a neural stem cell marker (Sox2). Expression was assessed in nonneoplastic and neoplastic ocular tissues collected from enucleated eyes of patients with retinoblastoma. During qualitative data interpretation, evaluating pathologists were masked to patient grouping. Results Expression of VEGF-A and VEGFR-2 in noninvasive (non–high-risk feature) retinoblastoma tumors was lower than in the invasive, or high-risk feature tumors. Moreover, our data indicate that the tumor cells, and not the surrounding stroma, secrete VEGF-A and that angiogenesis is mostly localized to the iris. Finally, our data showed that the expression of the neural stem cell marker Sox2 is associated with eyes with increased VEGF-A expression and tumor invasiveness. Conclusions Increased expression of angiogenic factors, with a concomitant increase in expression of the stem cell marker Sox2 observed in retinoblastoma tissues, may partially explain the aggressiveness of these tumors. The complex interaction of angiogenic and stem cell–related pathways in these tumors, especially in high-risk feature retinoblastoma, suggests that targeting tumor cells capable of secreting vasculogenic factors, as well as proangiogenic genes and signaling pathways, may be necessary for development of effective antimetastatic retinoblastoma drugs.

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Expression of Vascular Endothelial Growth Factor in Retinoblastoma

Areán

Orellana²,

Abourbih³

et al. 2010

Arch Ophthalmol

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To investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) and to determine its possible association with tumor differentiation status, optic nerve and/or choroidal invasion, anterior chamber invasion, vitreous seeding, and basophilic staining of the vascular walls.Methods: A retrospective study was performed to identify the expression of VEGF in 47 of 129 consecutive patients with retinoblastoma treated at the

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Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma

Cited by 52 publications

References 38 publications

Contrast-Enhancement of the Anterior Eye Segment in Patients with Retinoblastoma: Correlation between Clinical, MR Imaging, and Histopathologic Findings

Contrast-Enhancement of the Anterior Eye Segment in Patients with Retinoblastoma: Correlation between Clinical, MR Imaging, and Histopathologic Findings

Expression of Angiogenic Factors in Invasive Retinoblastoma Tumors Is Associated With Increase in Tumor Cells Expressing Stem Cell Marker Sox2

Expression of Vascular Endothelial Growth Factor in Retinoblastoma

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