Histopathological spectrum of common aldosterone-driver gene mutations in aldosterone-producing adenomas
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10499111" target="_blank" >RIV/00179906:_____/25:10499111 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/25:10499111
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=H.FOXaN8JQ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=H.FOXaN8JQ</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fmed.2025.1569619" target="_blank" >10.3389/fmed.2025.1569619</a>
Alternative languages
Result language
angličtina
Original language name
Histopathological spectrum of common aldosterone-driver gene mutations in aldosterone-producing adenomas
Original language description
Past studies on common mutant aldosterone-producing adenomas (APAs) had found genotype-phenotype correlations associated with histological appearance. Most of these studies did not perform CYP11B2-guided sequencing of APAs or sequencing for all the currently known aldosterone-driver genes. Hence, misinterpretation of 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. A total of 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, beta-catenin, and LHCGR antibody. Interestingly, APAs with a p.Thr41Ala CTNNB1 mutation also harbored a p.Val1373Met CACNA1D mutation. The CTNNB1 double mutant APAs 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 beta-catenin expression with prominent nuclear staining that reflects the constitutive activation of the Wnt/beta-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 notion that CYP11B2-guided sequencing of all currently known aldosterone-driver genes can fine-tune existing genotype-phenotype correlations in histopathological profiles.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Medicine
ISSN
2296-858X
e-ISSN
2296-858X
Volume of the periodical
12
Issue of the periodical within the volume
JUN
Country of publishing house
CH - SWITZERLAND
Number of pages
10
Pages from-to
1569619
UT code for WoS article
001513624200001
EID of the result in the Scopus database
2-s2.0-105009284027