Endocrine Abstracts

CYP11B2 is a key enzyme of primary aldosteronism, and several factors are involved in the regulation of CYP11B2 expression and the overproduction of aldosterone. Somatic mutations in aldosterone-driver genes are strongly associated with CYP11B2 expression and have been only detected in the CYP11B2-positive tumor area, indicating that aldosterone producing adenoma (APA) intratumoral heterogeneity corresponds to non-uniform CYP11B2 expression in neoplastic cells. In addition, CYP11B2 can contribute to the clinical diagnosis of primary aldosteronism. CYP11B2 has the potential to synthesize hybrid steroids, which is a unique and characteristic behavior of APA that is distinctive from bilateral hyperaldosteronism (BHA). However, the pathophysiology of primary aldosteronism in both APA and non-neoplastic subtypes remains controversial.

Objective: Our aim in the present study was to compare immunohistochemical (IHC) CYP11B2 and CYP11B1 staining in adrenal slices to histological diagnosis based on H&E staining.

Materials and method: Retrospective evaluation adrenal tumors from patients with primary aldosteronism (n = 20). According to CT unilateral macrohyperplasia was detected in 19 patients (95% of total), all of them were confirmed to have unilateral hyperproduction of aldosterone according to AVS. Both H&E and immunohistochemical expression of CYP11B2 and CYP11B1 (mouse monoclonal anti-human CYP11B2 primary antibodies and rat monoclonal anti-human CYP11B1); were analyzed in 3.5 mm thick adrenal slices in one representative slide from each case. In addition to IHC analysis of aldosterone-producing adenomas (APAs) and hyperplasia, small extranodular CYP11B2 positive cell clusters, so-called aldosterone-producing cell clusters (APCCs) were identified.

Results: Immunohistochemistry studies of the resected adrenals from 20 patients with PA operated due to unilateral production of aldosterone using CYP11B2 and CYP11B1 staining showed that 10 of those with an adenoma on CT scanning showed CYP11B2 and CYP11B1 staining in the adenoma. Furthermore, 5 cases of an unilateral adenoma, showed CYP11B2 and CYP11B1 staining in the adjacent adrenal cortex and an absence of staining for CYP11B2 in the adenoma. 5 cases showed CYP11B2 expression is heterogeneously immunolocalized throughout the tumor area.

Conclusions: Thus, the functional heterogeneity of adrenal tumors in primary aldosteronism has been proven. IHC staining of adrenal tissue improves subtype diagnostics of primary aldosteronism.