Pathophysiological significance of CYP11B2 immunohistochemical staining in primary aldosteronism

K. Nanba; M. Tsuiki; K. Sawai; K. Mukai; K. Nakao; T. Tamanaha; T. Usui; T. Tagami; H. Okuno; T. Yamamoto; A. Shimatsu; M. Naruse

Background: Although primary aldosteronism (PA) is the common cause of hypertension subjected to surgery, methods of pathological confirmation of aldosterone overproduction have not been established. Aim of the study was to investigate immunohistochemically the expression of CYP11B2 in the adrenal tissue of PA.

Methods: Twenty five patients with PA including 20 patients with aldosterone-producing adenoma (APA) and 5 patients without APA (non-APA) were studied. Immunohistochemical staining was performed with anti-CYP11B2 on paraffin-embedded sections. We analyzed the expression of CYP11B2 semi-quantitatively by scoring the staining intensity from (− or ±) to (2+).

Results: Eighty five % of the patients with APA showed positive immunostaining for CYP11B2 in the adrenal tumor. Tumor volume estimated from the diameter was negatively correlated with CYP11B2 score (P<0.001) and positively correlated with basal aldosterone to renin ratio (ARR) (P<0.001). CYP11B2 score adjusted by the tumor volume was correlated positively with ARR (P<0.01) and negatively with serum potassium (P<0.05). In addition to the immunostaining in the tumor, there existed cell clusters of positive immunostaining of CYP11B2 (APCC) in the adjacent tissues. Although the APCC was seen in the adjacent tissue of APA, the number of APCC was significantly larger in patients with non-APA than those with APA (P<0.001). Serum potassium was significantly lower (P=0.01) and number of anti-hypertensive drug (P<0.05), prevalence of hypokalemia (P=0.001), plasma aldosterone concentration (P=0.001), and ARR (P<0.01) were significantly higher in patients with APA than those with non-APA.

Conclusions: The present study clearly demonstrated that CYP11B2 immunostaining is useful for the histopathological confirmation of aldosterone production and that both CYP11B2 expression and tumor volume could contribute to the extent of hyperaldosteronism in APA. In addition, increased number of APCC in the non-tumorous adrenocortical tissues could cause aldosterone excess in patients with non-APA.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Endocrine Abstracts

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