Details

Autor(en) / Beteiligte

• Monticone, Silvia
• Castellano, Isabella
• Versace, Karine
• Lucatello, Barbara
• Veglio, Franco
• Gomez-Sanchez, Celso E.
• Williams, Tracy A.
• Mulatero, Paolo

Titel

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

Ist Teil von

• Molecular and cellular endocrinology, 2015-08, Vol.411, p.146-154

Ort / Verlag

Ireland: Elsevier Ireland Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• •Somatic mutations in genes involved in Ca2+ homeostasis cause 60% of sporadic APAs.•KCNJ5-mutated APAs are composed mainly of zona fasciculata-like cells.•ATPase and CACNA1D-mutated APAs are composed mainly of zona glomerulosa-like cells.•Nodules with high CYP11B2 expression are small and composed mainly of ZG-like cells. 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.