Histopathological spectrum of common aldosterone-driver gene mutations in aldosterone-producing adenomas

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11150/25:10499111

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Histopathological spectrum of common aldosterone-driver gene mutations in aldosterone-producing adenomas

Popis výsledku v původním jazyce

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&amp;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.

Název v anglickém jazyce

Histopathological spectrum of common aldosterone-driver gene mutations in aldosterone-producing adenomas

Popis výsledku anglicky

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&amp;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Medicine

ISSN

2296-858X

e-ISSN

2296-858X

Svazek periodika

12

Číslo periodika v rámci svazku

JUN

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

10

Strana od-do

1569619

Kód UT WoS článku

001513624200001

EID výsledku v databázi Scopus

2-s2.0-105009284027