Format

Send to

Choose Destination
Mol Cell Endocrinol. 2015 Aug 15;411:146-54. doi: 10.1016/j.mce.2015.04.022. Epub 2015 May 6.

Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas.

Author information

1
Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino, Italy. Electronic address: smv.monticone@gmail.com.
2
Division of Pathology, Department of Medical Sciences, University of Torino, Torino, Italy.
3
Division of Radiology, University of Torino, Torino, Italy.
4
Division of Endocrinology, Department of Medical Sciences, University of Torino, Torino, Italy.
5
Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino, Italy.
6
Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS 39216, USA.
7
Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino, Italy. Electronic address: paolo.mulatero@libero.it.

Abstract

Adrenal glands removed for unilateral primary aldosteronism (PA) display marked histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D can partially account for these differences. In this study we aimed at combining phenotypic and genotypic characteristics, integrating genetic and immunohistochemistry correlates in sporadic PA. Seventy-one adrenal glands have been included in the study and analyzed for mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. Histological examination and immunohistochemical staining for CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) were performed on aldosterone-producing adenomas (APAs) and adjacent adrenal cortex. In our cohort, the final histopathological diagnosis was multinodular hyperplasia in 22.5% of the patients and single nodule in 77.5%. Forty-five percent of the removed adrenals displayed extra-APA CYP11B2-positive cell nests (B2-CN). Among adrenal vein sampling parameters the suppression of contralateral adrenal was more frequent and the lateralization index was higher in the subgroup of patients without extra-APA B2-CN compared to the subgroup with extra-APA B2-CN. KCNJ5-mutated APAs were composed mainly of zona fasciculata-like cells with high expression of CYP11B1, while ATP1A1, ATP2B3 and CACNA1D-mutated APAs presented more frequently a zona-glomerulosa-like phenotype with high expression of CYP11B2. We observed a significant inverse correlation between CYP11B2 expression and the size of the nodules and, if CYP11B2 expression was corrected for tumor volume, a significant correlation with plasma aldosterone and aldosterone to renin ratio. Our findings indicate that combination of genotyping and immunohistochemistry improves the final histopathological diagnosis between single nodule and multinodular hyperplasia of the assessed adrenals.

KEYWORDS:

ATP1A1; Aldosterone producing adenoma; CACNA1D; CYP11B1 immunohistochemistry; CYP11B2 immunohistochemistry; KCNJ5

PMID:
25958045
PMCID:
PMC4474471
DOI:
10.1016/j.mce.2015.04.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center