title: Functional histopathological markers of aldosterone producing adenoma and somatic KCNJ5 mutations.
abstract: The current pathological diagnosis of Aldosterone Producing Adenoma (APA) is limited to the description of nodules and/or hyperplasia in the resected adrenal gland, independent of their functional characteristics. The aim of our study was to characterize histopathological markers to confirm the presence and identify the sites of aldosterone production and to discriminate KCNJ5-related APA. We investigated 18 adrenals with APA and 15 with non-functioning adrenal incidentaloma (NFAI) for expression of Disabled-2 and GIRK4, two markers of zona glomerulosa (ZG), and 77 adrenals with APA with known mutational status for GIRK4 expression. Two-thirds of APA and only one NFAI exhibited both GIRK4 and Disabled-2 membrane staining, allowing to correctly classify 79% of adenomas. Remarkably, 28/32 APA with KCNJ5 mutations exhibited lower GIRK4 expression in APA relative to peritumoral ZG. This was highly specific for KCNJ5 mutations, indicating that GIRK4 immunohistochemistry might be used for initial screening of the somatic mutation status.
authors.affiliation: INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Fabio Luiz
authors.initials: FL
authors.lastname: Fernandes-Rosa
authors.affiliation: INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France; Inserm, U1016, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tissier
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France; Inserm, U1016, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital Cochin, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.affiliation: INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Tchao
authors.initials: T
authors.lastname: Meatchi
authors.affiliation: INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.affiliation: INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France; University Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: sheerazed.boulkroun@inserm.fr.
authors.forename: Sheerazed
authors.initials: S
authors.lastname: Boulkroun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000310:Adrenal Gland Neoplasms / Q000473:pathology; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015384:Zona Glomerulosa / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C102885:DAB2 protein, human; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D025521:Tumor Suppressor Proteins; D000450:Aldosterone
keywords: Aldosterone producing adenoma; Immunohistological diagnosis; Potassium channels; Primary aldosteronism