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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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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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