{"doi":"10.1210/clinem/dgae411","title":"Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism","abstract":"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.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2024,"id":442667,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1256426,"name":"Livia Lenzini","orcid":"0000-0001-6146-3015","position":1,"is_corresponding":false},{"id":1256427,"name":"Giulio Ceolotto","orcid":"0000-0002-4687-8033","position":2,"is_corresponding":false},{"id":1256878,"name":"Francesca Gioco","orcid":null,"position":3,"is_corresponding":false},{"id":1256428,"name":"Andrea Benetti","orcid":"0000-0002-9316-8392","position":4,"is_corresponding":false},{"id":1256429,"name":"Alessandra Giannella","orcid":"0000-0002-4464-9800","position":5,"is_corresponding":false},{"id":1256430,"name":"Hala Ajjour","orcid":"0009-0002-8238-9971","position":6,"is_corresponding":false},{"id":1256431,"name":"Francesca Galuppini","orcid":"0000-0002-3245-2322","position":7,"is_corresponding":false},{"id":1256432,"name":"Gianmaria Pennelli","orcid":"0000-0003-0210-165X","position":8,"is_corresponding":false},{"id":1256433,"name":"Teresa Maria Seccia","orcid":"0000-0002-3639-4086","position":9,"is_corresponding":false},{"id":185064,"name":"Celso E. Gomez-Sanchez","orcid":"0000-0002-9882-2082","position":10,"is_corresponding":false},{"id":1256434,"name":"Gian Paolo Rossi","orcid":"0000-0002-7963-0931","position":11,"is_corresponding":false},{"id":1256425,"name":"Brasilina Caroccia","orcid":"0000-0002-3775-0011","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T02:01:20.107161Z","pmid":"38888173","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}