Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.

Autor:	Caroccia B; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.; Department of Women's and Children's Health-SBD, University of Padua, Padua 35122, Italy., Lenzini L; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy., Ceolotto G; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy., Gioco F; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy., Benetti A; Division of Thrombotic and Hemorrhagic Diseases, Department of Medicine-DIMED, University of Padua, Padua 35122, Italy., Giannella A; Division of Thrombotic and Hemorrhagic Diseases, Department of Medicine-DIMED, University of Padua, Padua 35122, Italy., Ajjour H; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy., Galuppini F; Department of Medicine, Surgical Pathology Unit, University of Padua, Padua 35122, Italy., Pennelli G; Department of Medicine, Surgical Pathology Unit, University of Padua, Padua 35122, Italy., Seccia TM; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy., Gomez-Sanchez C; G.V. (Sonny) Montgomery VA Medical Center and Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA., Rossi GP; Specialized Center of Excellence for Hypertension of the European Society of Hypertension and Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua 35126, Italy.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Sep 16; Vol. 109 (10), pp. 2433-2443.
DOI:	10.1210/clinem/dgae411
Abstrakt:	Context: The search for somatic mutations in adrenals resected from patients with primary aldosteronism (PA) is performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas. Objective: To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next-generation sequencing (NGS). Methods: We investigated 127 consecutive adrenal aldosterone-producing adenomas from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, by Sanger sequencing and NGS. Results: Double IHC for CYP11B2 and CYP11B1 revealed 3 distinct patterns: CYP11B2-positive adenoma (pattern 1), mixed CYP11B1/CYP11B2-positive adenoma (pattern 2), and adrenals with multiple small CYP11B2-positive nodules (pattern 3). Sanger sequencing allowed detection of KCNJ5 mutations in 44% of the adrenals; NGS revealed such mutations in 10% of those negative at Sanger and additional mutations in 61% of the cases. Importantly the rate of KCNJ5 mutations differed across patterns: 17.8% in pattern 1, 71.4% in pattern 2, and 10.7% in pattern 3 (χ2 = 22.492, P < .001). Conclusion: NGS allowed detection of mutations in many adrenals that tested negative at Sanger sequencing. Moreover, the different distribution of KCNJ5 mutations across IHC patterns indicates that IHC-guided sequencing protocols selecting CYP11B2-positive areas could furnish results that might not be representative of the entire mutational status of the excised adrenal, which is important at a time when KCNJ5 mutations are suggested to drive management of patients with aldosterone-producing adenomas. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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