Abstract 401: Immuno-phenotypic Characterization of Lateralized Primary Aldosteronism with New Monoclonal Antibodies against the Human Aldosterone Synthase (CYP11B2) and 11- beta hydroxylase (CYP11B1)
Background: Primary Aldosteronism (PA) is commonly due to an Aldosterone-Producing Adenoma (APA), but until now the lack of a specific antibody for human aldosterone synthase (hCYP11B2) has prevented the identification of APA in the excised adrenal gland.
Objectives: To investigate the usefulness of a novel monoclonal antibody for hCYP11B2 for the immuno-phenotypic characterization of a large series of consecutive adrenal glands from APA patients diagnosed by the “four corners criteria” fully characterized for KCNJ5 mutations.
Methods: To generate the antibodies, spleen cells from mice immunized with peptides against hCYP11B2 were fused to mouse myeloma cells. CYP11B2 and CYP11B1 were detected with immunohistochemistry in the adrenals from 49 consecutive APA patients. Based on results of a pilot study the following classification was developed: Pattern1: adenoma with uniform CYP11B2 staining + few areas of CYP11B1 staining; Pattern2: adenoma with diffuse CYP11B2 staining + few areas of CYP11B1 staining + some cells co-expressing CYP11B2/CYP11B1; Pattern3: adenoma expressing CYP11B1 + clusters of cells CYP11B2; Pattern4: no adenoma + multiple clusters of sub-capsular CYP11B2 cells; Pattern5: multi-nodular adrenal cortex + clusters of sub-capsular CYP11B2 cells.
Results: KCNJ5 mutations were found in 38% of the cases (19/49). With CYP11B2/CYP11B1 immunostaining the following results were found: pattern 1 16.3% (8/49); pattern2 32.7% (15/49); pattern 3 16.3% (7/49); pattern 4 22.4% (10/49); pattern 5 12.2% (5/49).
Conclusions: The highly variable steroidogenic enzymes (CYP11B2, CYP11B1) expression in a series of consecutive APA show the existence of at least 5 different patterns, thus challenging the classical notion that PA entails only APA or bilateral hyperplasia.
Author Disclosures: F. Gioco: None. C. Gomez-Sanchez: None. A. Fassina: None. X. Qi: None. C. Velarde-Miranda: None. G. Rossitto: None. E. Gomez-Sanchez: None. G. Rossi: None.
- © 2014 by American Heart Association, Inc.