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Angiogenesis in Human Normal and Pathologic Adrenal Cortex

Departments of Internal Medicine (G.P.B., A.M., A.S.), Oncology (A.G.B., M.M., P.V., A.G.N.), and Surgery (P.I., P.M.), University of Pisa, 56100 Pisa, Italy

Address all correspondence and requests for reprints to: Bernini Giampaolo, Department of Internal Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy. E-mail: g.bernini{at}med.unipi.it.

Abstract

The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 ± 27.8) than in N (336.6 ± 14.5), APA (322.8 ± 19.1), CPA (288.5 ± 14.3), and NFA (274.2 ± 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 ± 2.1) than in APA (56.5 ± 7.5), CPA (38.5 ± 7.0), N (33.1 ± 6.1), and NFA (0.76 ± 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found.

In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.

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