Aldosterone-Producing Adenomas Histopathology-Genotype Correlation and Identification of a Novel CACNA1D Mutation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F17%3A10363668" target="_blank" >RIV/00216208:11150/17:10363668 - isvavai.cz</a>

Alternative codes found

RIV/00179906:_____/17:10363668

Result on the web

<a href="http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09057" target="_blank" >http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09057</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09057" target="_blank" >10.1161/HYPERTENSIONAHA.117.09057</a>

Result language

angličtina

Original language name

Aldosterone-Producing Adenomas Histopathology-Genotype Correlation and Identification of a Novel CACNA1D Mutation

Original language description

Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 are thought to cause the excessive autonomous aldosterone secretion of aldosterone-producing adenomas (APAs). The histopathology of KCNJ5 mutant APAs, the most common and largest, has been thoroughly investigated and shown to have a zona fasciculata-like composition. This study aims to characterize the histopathologic spectrum of the other genotypes and document the proliferation rate of the different sized APAs. Adrenals from 39 primary aldosteronism patients were immunohistochemically stained for CYP11B2 to confirm diagnosis of an APA. Twenty-eight adenomas had sufficient material for further analysis and were target sequenced at hot spots in the 5 causal genes. Ten adenomas had a KCNJ5 mutation (35.7%), 7 adenomas had an ATP1A1 mutation (25%), and 4 adenomas had a CACNA1D mutation (14.3%). One novel mutation in exon 28 of CACNA1D (V1153G) was identified. The mutation caused a hyperpolarizing shift of the voltage-dependent activation and inactivation and slowed the channel&apos;s inactivation kinetics. Immunohistochemical stainings of CYP17A1 as a zona fasciculata cell marker and Ki67 as a proliferation marker were used. KCNJ5 mutant adenomas showed a strong expression of CYP17A1, whereas ATP1A1/CACNA1D mutant adenomas had a predominantly negative expression (P value =1.20x10(-4)). ATP1A1/CACNA1D mutant adenomas had twice the nuclei with intense staining of Ki67 than KCNJ5 mutant adenomas (0.7% [0.5%-1.9%] versus 0.4% [0.3%-0.7%]; P value = 0.04). Further, 3 adenomas with either an ATP1A1 mutation or a CACNA1D mutation had &gt;30% nuclei with moderate Ki67 staining. In summary, similar to KCNJ5 mutant APAs, ATP1A1 and CACNA1D mutant adenomas have a seemingly specific histopathologic phenotype.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Hypertension

ISSN

0194-911X

e-ISSN

—

Volume of the periodical

70

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

8

Pages from-to

129-136

UT code for WoS article

000402880500022

EID of the result in the Scopus database

2-s2.0-85020144818