BRIEF RESEARCH REPORT article
Front. Med.
Sec. Pathology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1569619
This article is part of the Research TopicEnhancing Adrenal Tumor Diagnostics: Biomarkers and Molecular MechanismsView all 12 articles
Histopathological spectrum of common aldosterone-driver gene mutant aldosterone-producing adenomas (APAs)
Provisionally accepted
Fatin Athirah Pauzi1
MUAATAMARULAIN MUSTANGIN1
Geok Chin Tan1
Ales Ryska2Jiri Ceral2
Miroslav Solař2
Elena Aisha Azizan1*- 1Faculty of Medicine, National University of Malaysia, Cheras, Malaysia
- 2Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czechia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Past studies on common mutant aldosterone-producing adenomas (APAs) had found genotypephenotype correlations associating with histological appearance. Most of these studies did not perform CYP11B2-guided sequencing of the APA or sequencing for all the currently known aldosterone-driver genes. Hence misinterpretation on the genotype-phenotype correlations could have occurred. Herein, we aimed to identify the genotype-phenotype correlations associated with the histopathology of the different mutant APAs utilizing CYP11B2-guided sequencing. 33 APAs with confirmed aldosterone-driver mutation (17 KCNJ5 mutant APAs, 8 ATP1A1 mutant APAs, 6 CACNA1D mutant APAs, and 2 CTNNB1 mutant APAs) were immunohistochemically stained using H&E, CYP17A1, CYP11B2, KCNJ5, Ki67, β-catenin and LHCGR antibody. Interestingly, the APA with a p.Thr41Ala CTNNB1 mutation, also harbored a p.Val1373Met CACNA1D mutation. The CTNNB1 double mutant APA had less expression of CYP17A1 and larger quantities of spironolactone bodies than a single mutant APA with a p.Ser45Phe CTNNB1 mutation. However, both CTNNB1 mutant APAs displayed diffuse active β-catenin expression with prominent nuclear staining that reflects the constitutive activation of the Wnt/β-catenin signaling pathway (p=0.016 compared to other genotypes) but no significant increase in LHCGR. KCNJ5 mutant APAs displayed distinct existence of atypical cells (6 of the 17 KCNJ5 mutant APAs), whereas CACNA1D mutant APAs had frequent presentations of spironolactone bodies (4 of the 6 CACNA1D mutant APAs), and ATP1A1 mutant APAs had significantly higher Ki67 score than KCNJ5 mutant APAs (p=0.020). The results of this study support the suggestion that CYP11B2-guided sequencing of all the currently known aldosterone-driver genes can fine tune current genotype-phenotype histopathology profiles.Formatted: Highlight
Keywords: Aldosterone-producing adenomas, CYP11B2-guided sequencing, aldosterone-driver mutation, genotype-phenotype correlations, Immunohistochemistry
Received: 01 Feb 2025; Accepted: 17 Apr 2025.
Copyright: © 2025 Pauzi, MUSTANGIN, Tan, Ryska, Ceral, Solař and Azizan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Elena Aisha Azizan, Faculty of Medicine, National University of Malaysia, Cheras, Malaysia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.