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Histological characterization of aldosterone-producing adrenocortical adenomas with different somatic mutations


Ono, Yoshikiyo; Yamazaki, Yuto; Omata, Kei; Else, Tobias; Tomlins, Scott A; Rhayem, Yara; Williams, Tracy Ann; Reincke, Martin; Carling, Tobias; Monticone, Silvia; Mulatero, Paolo; Beuschlein, Felix; Ito, Sadayoshi; Satoh, Fumitoshi; Rainey, William E; Sasano, Hironobu (2020). Histological characterization of aldosterone-producing adrenocortical adenomas with different somatic mutations. Journal of Clinical Endocrinology & Metabolism, 105(3):dgz235.

Abstract

CONTEXT
Aldosterone-producing adrenocortical adenomas (APAs) are mainly composed of clear (lipid rich) and compact (eosinophilic) tumor cells. The detailed association between these histological features and somatic mutations (KCNJ5, ATP1A1, ATP2B3 and CACNA1D) in APAs is unknown.
OBJECTIVE
To examine the association between histological features and individual genotypes in APAs.
METHODS
Examination of 39 APAs subjected to targeted next-generation sequencing (11 KCNJ5, 10 ATP1A1, 10 ATP2B3, and 8 CACNA1D) and quantitative morphological and immunohistochemical (CYP11B2 and CYP17A1) analyses using digital imaging software.
RESULTS
KCNJ5- and ATP2B3-mutated APAs had clear cell dominant features [KCNJ5: clear 59.8% (54.4%-64.6 %) vs. compact 40.2% (35.4%-45.6 %), P=0.0022; ATP2B3: clear 54.3% (48.2%-62.4 %) vs. compact 45.7% (37.6%-51.8 %), P=0.0696]. ATP1A1- and CACNA1D-mutated APAs presented with marked intratumoral heterogeneity. A significantly positive correlation of immunoreactivity was detected between CYP11B2 and CYP17A1 in tumor cells of KCNJ5-mutated APAs (P=0.0112; ρ=0.7237) , in contrast, significantly inverse correlation was detected in ATP1A1-mutated APAs (P=0.0025; ρ=-0.8667).
CONCLUSION
KCNJ5-mutated APAs, co-expressing CYP11B2 and CYP17A1, were more deviated in terms of zonation-specific differentiation of adrenocortical cells compared with ATP1A1- and ATP2B3- mutated APAs.

Abstract

CONTEXT
Aldosterone-producing adrenocortical adenomas (APAs) are mainly composed of clear (lipid rich) and compact (eosinophilic) tumor cells. The detailed association between these histological features and somatic mutations (KCNJ5, ATP1A1, ATP2B3 and CACNA1D) in APAs is unknown.
OBJECTIVE
To examine the association between histological features and individual genotypes in APAs.
METHODS
Examination of 39 APAs subjected to targeted next-generation sequencing (11 KCNJ5, 10 ATP1A1, 10 ATP2B3, and 8 CACNA1D) and quantitative morphological and immunohistochemical (CYP11B2 and CYP17A1) analyses using digital imaging software.
RESULTS
KCNJ5- and ATP2B3-mutated APAs had clear cell dominant features [KCNJ5: clear 59.8% (54.4%-64.6 %) vs. compact 40.2% (35.4%-45.6 %), P=0.0022; ATP2B3: clear 54.3% (48.2%-62.4 %) vs. compact 45.7% (37.6%-51.8 %), P=0.0696]. ATP1A1- and CACNA1D-mutated APAs presented with marked intratumoral heterogeneity. A significantly positive correlation of immunoreactivity was detected between CYP11B2 and CYP17A1 in tumor cells of KCNJ5-mutated APAs (P=0.0112; ρ=0.7237) , in contrast, significantly inverse correlation was detected in ATP1A1-mutated APAs (P=0.0025; ρ=-0.8667).
CONCLUSION
KCNJ5-mutated APAs, co-expressing CYP11B2 and CYP17A1, were more deviated in terms of zonation-specific differentiation of adrenocortical cells compared with ATP1A1- and ATP2B3- mutated APAs.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Biochemistry
Life Sciences > Endocrinology
Life Sciences > Clinical Biochemistry
Health Sciences > Biochemistry (medical)
Language:English
Date:1 March 2020
Deposited On:15 Jan 2020 15:55
Last Modified:29 Jul 2020 12:39
Publisher:Oxford University Press
ISSN:0021-972X
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1210/clinem/dgz235
PubMed ID:31789380

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