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Int. J. Mol. Sci. 2014, 15(4), 5323-5336; doi:10.3390/ijms15045323
Article

Role of VEGF-A and Its Receptors in Sporadic and MEN2-Associated Pheochromocytoma

1,†
,
1,†
,
1
,
1
,
2
,
2
,
1
 and
1,*
1 Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil 2 Pathology Department, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Rio Grande do Sul, Brazil These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 22 January 2014 / Revised: 18 March 2014 / Accepted: 18 March 2014 / Published: 26 March 2014
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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Abstract

Pheochromocytoma (PHEO), a rare catecholamine producing tumor arising from the chromaffin cells, may occurs sporadically (76%–80%) or as part of inherited syndromes (20%–24%). Angiogenesis is a fundamental step in tumor proliferation and vascular endothelial growth factor (VEGF-A) is the most well-characterized angiogenic factor. The role of angiogenic markers in PHEO is not fully understood; investigations were therefore made to evaluate the expression of VEGF-A and its receptors in PHEO and correlate to clinical parameters. Twenty-nine samples of PHEO were evaluated for VEGF-A, VEGF receptor-1 (VEGFR-1) VEGFR-2 expression and microvessel density (MVD) by immunohistochemistry. Clinical data were reviewed in medical records. The mean age of patients was 38 ± 14 years, and 69% were woman. VEGF-A, VEGFR-1 and VEGFR-2 staining were detected in nearly all PHEO samples. No significant correlation was observed between VEGF-A, VEGFR-1, VEGFR-2 expression or MVD and age at diagnosis, tumor size or sporadic and hereditary PHEO. However, the levels of expression of these molecules were significantly higher in malignant PHEO samples (p = 0.027, p = 0.003 and p = 0.026, respectively).VEGF-A and its receptors were shown to be up-regulated in malignant PHEO, suggesting that these molecules might be considered as therapeutic targets for unresectable or metastatic tumors.
Keywords: pheocromocytoma; VEGF-A; microvessel density pheocromocytoma; VEGF-A; microvessel density
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Ferreira, C.V.; Siqueira, D.R.; Romitti, M.; Ceolin, L.; Brasil, B.A.; Meurer, L.; Capp, C.; Maia, A.L. Role of VEGF-A and Its Receptors in Sporadic and MEN2-Associated Pheochromocytoma. Int. J. Mol. Sci. 2014, 15, 5323-5336.

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