Angiogenesis in human normal and pathologic adrenal cortex.
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.
Bernini
G P
GP
Department of Internal Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy. g.bernini@med.unipi.it
Moretti
A
A
Bonadio
A G
AG
Menicagli
M
M
Viacava
P
P
Naccarato
A G
AG
Iacconi
P
P
Miccoli
P
P
Salvetti
A
A
D000236:Adenoma / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism; D000302:Adrenal Cortex / Q000098:blood supply*; D000306:Adrenal Cortex Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000378:metabolism; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000096:biosynthesis / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001808:Blood Vessels / Q000473:pathology; D016228:Endothelial Growth Factors / Q000032:analysis; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008833:Microcirculation / Q000033:anatomy & histology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012083:Renin / Q000097:blood; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000450:Aldosterone; D012083:Renin; D006854:Hydrocortisone