Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.
J Clin Endocrinol Metab
; 2024 Jun 18.
Article
em En
| MEDLINE
| ID: mdl-38888173
ABSTRACT
CONTEXT The search for somatic mutations in adrenals resected from primary aldosteronism (PA) patients is being 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 adenoma from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, 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<0.001).CONCLUSIONS:
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 APA patient.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article