ECE2015 Guided Posters Endocrine tumours and neoplasia – Adrenal Tumour (7 abstracts)
Immunoexpressions of CYP11B2 and HSD3B2 in genetically characterised aldosterone producing adenomas
Christian Gebhard 1 , Yara Rhayem 1 , Anna Dietz 1 , Anna Riester 1 , Constanze Hantel 1 , Marion Schuster 1 , Tim M Strom 2, , Celso Gomez-Sanchez 4, , Martin Reincke 1 & Felix Beuschlein 1
1Medizinische Klinik und Poliklinik IV, Ludwig‐Maximilians‐University, Munich, Germany; 2Institute of Human Genetics, Helmholtz Zentrum Munich, Munich, Germany; 3Institute of Human Genetics, Technische Universität München, Munich, Germany; 4Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center, Jackson, Mississippi, USA; 5Department of Medicine‐Endocrinology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Primary aldosteronism caused by aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia is the most prevalent cause of secondary hypertension. Somatic mutations of KCNJ5, ATP1A1, CACNA1D and ATP2B3 have been shown to be involved in the formation of APA. We studied the immunoexpressions of CYP11B2 and HSD3B2, the rate-limiting enzyme for aldosterone production and the prevalent isoform of β-HSD found in APA respectively, and correlated these findings with the mutation status, histopathology of APA and to the biochemical and clinical outcome of adrenalectomy. In our study, APA tissues obtained by adrenalectomy were divided into five subgroups (KCNJ5, ATP1A1, CACNA1D, ATP2B3 or WT) after characterization of the respective mutational status by direct or exome sequencing. Paraffin-embedded tumors were evaluated for size and cell composition. Immunolocalization and semi-quantitative immunoexpressions of CYP11B2 and HSD3B2 were analysed. Scoring staining intensity was determined along with clinical findings. Our results show that a majority of APAs consists of both zona fasciculata-like and zona glomerulosa (ZG)-like cells. CACNA1D mutated-APA were significantly smaller than KCNJ5 mutated-APA (P<0.05). All mutated APAs presented CYP11B2 positive clusters or variably stained scattered cells while WT APAs were weakly or negatively stained for CYP11B2 with only clusters in adjacent ZG. H-Score for CYP11B2 was significantly different between WT and KCNJ5 mutated APAs (P<0.05). Immunoreactivity of HSD3B2 was strongly present in all analyzed tissues independently of the tumoural cell type and no significant difference was noted between the subgroups’ HSD3B2 H-scores. Biochemically, serum potassium levels of all patients were normalized after adrenalectomy. High aldosterone to renin ratio at diagnosis and shorter duration of hypertension preceding surgery were associated with better clinical outcome. Our findings suggest that KCNJ5 and not ATP1A1, CACNA1D or ATP2B3 mutated APAs have significantly different CYP11B2 immunoreactivity, compared with WT-APA while immunoreacivities of HSD3B2 or CYP11B2 are not correlated with outcome.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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