Histopathological diagnosis of primary aldosteronism using CYP11B2 immunohistochemistry

Kazutaka Nanba, Mika Tsuiki, Kuniko Sawai, Kuniaki Mukai, Koshiro Nishimoto, Takeshi Usui, Tetsuya Tagami, Hiroshi Okuno, Tetsuro Yamamoto, Akira Shimatsu, Takuyuki Katabami, Ataru Okumura, Gen Kawa, Akiyo Tanabe, Mitsuhide Naruse

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Abstract

Context: Although primary aldosteronism (PA) is the most common cause of endocrine hypertension, histopathological methods to reveal the presence and sites of aldosterone overproduction remain to be established. Objective: The objective of the study was to investigate the significance of immunohistochemical staining to detect CYP11B2 and CYP11B1 in adrenal tissue of patients with PA. Design and Patients: Thirty-two patients with PA who underwent unilateral adrenalectomy were studied. Immunohistochemical staining was performed using anti-CYP11B2 and anti-CYP11B1 antibodies on paraffin-embedded sections. We analyzed the expression of each enzyme semiquan-titatively by scoring staining intensity and correlating it with clinical findings. Results: Twenty-two patients showed positive CYP11B2 immunostaining in their tumors (aldosterone producing adenoma, APA). Four patients with CYP11B2-negative unilateral adenomas and 4 patients without tumors on computed tomography showed aldosterone-producing cell clusters (APCCs) with CYP11B2 immunostaining in the zona glomerulosa (multiple APCCs). The remaining 2 patients had unilateral multiple adrenocortical micronodules and diffuse adrenocortical hyperplasia, respectively. In APA, CYP11B2 score adjusted for tumor volume was positively correlated with plasma aldosterone and negatively correlated with serum potassium. The APA group was divided into 3 subgroups based on relative CYP11B2 and CYP11B1 immunostaining levels. The CYP11B2/CYP11B1-equivalent and CYP11B1-dominant APA groups showed significantly higher serum cortisol after 1 mg dexamethasone and larger tumor size than the CYP11B2-dominant APA group. Conclusions: The present study clearly demonstrates that CYP11B2 immunostaining is a powerful tool for histopathological diagnosis of aldosterone overproduction in PA and for subtype classification of APA, multiple APCCs, unilateral multiple adrenocortical micronodules, and diffuse hyperplasia.

Original languageEnglish
Pages (from-to)1567-1574
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number4
DOIs
Publication statusPublished - 2013 Apr

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Cytochrome P-450 CYP11B2
Hyperaldosteronism
Aldosterone
Immunohistochemistry
Steroid 11-beta-Hydroxylase
Adenoma
Tumors
Staining and Labeling
Hyperplasia
Zona Glomerulosa
Neoplasms
Adrenalectomy
Tumor Burden
Serum
Paraffin
Dexamethasone
Tomography

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Histopathological diagnosis of primary aldosteronism using CYP11B2 immunohistochemistry. / Nanba, Kazutaka; Tsuiki, Mika; Sawai, Kuniko; Mukai, Kuniaki; Nishimoto, Koshiro; Usui, Takeshi; Tagami, Tetsuya; Okuno, Hiroshi; Yamamoto, Tetsuro; Shimatsu, Akira; Katabami, Takuyuki; Okumura, Ataru; Kawa, Gen; Tanabe, Akiyo; Naruse, Mitsuhide.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 4, 04.2013, p. 1567-1574.

Research output: Contribution to journalArticle

Nanba, K, Tsuiki, M, Sawai, K, Mukai, K, Nishimoto, K, Usui, T, Tagami, T, Okuno, H, Yamamoto, T, Shimatsu, A, Katabami, T, Okumura, A, Kawa, G, Tanabe, A & Naruse, M 2013, 'Histopathological diagnosis of primary aldosteronism using CYP11B2 immunohistochemistry', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 4, pp. 1567-1574. https://doi.org/10.1210/jc.2012-3726
Nanba, Kazutaka ; Tsuiki, Mika ; Sawai, Kuniko ; Mukai, Kuniaki ; Nishimoto, Koshiro ; Usui, Takeshi ; Tagami, Tetsuya ; Okuno, Hiroshi ; Yamamoto, Tetsuro ; Shimatsu, Akira ; Katabami, Takuyuki ; Okumura, Ataru ; Kawa, Gen ; Tanabe, Akiyo ; Naruse, Mitsuhide. / Histopathological diagnosis of primary aldosteronism using CYP11B2 immunohistochemistry. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 4. pp. 1567-1574.
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AU - Nanba, Kazutaka

AU - Tsuiki, Mika

AU - Sawai, Kuniko

AU - Mukai, Kuniaki

AU - Nishimoto, Koshiro

AU - Usui, Takeshi

AU - Tagami, Tetsuya

AU - Okuno, Hiroshi

AU - Yamamoto, Tetsuro

AU - Shimatsu, Akira

AU - Katabami, Takuyuki

AU - Okumura, Ataru

AU - Kawa, Gen

AU - Tanabe, Akiyo

AU - Naruse, Mitsuhide

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N2 - Context: Although primary aldosteronism (PA) is the most common cause of endocrine hypertension, histopathological methods to reveal the presence and sites of aldosterone overproduction remain to be established. Objective: The objective of the study was to investigate the significance of immunohistochemical staining to detect CYP11B2 and CYP11B1 in adrenal tissue of patients with PA. Design and Patients: Thirty-two patients with PA who underwent unilateral adrenalectomy were studied. Immunohistochemical staining was performed using anti-CYP11B2 and anti-CYP11B1 antibodies on paraffin-embedded sections. We analyzed the expression of each enzyme semiquan-titatively by scoring staining intensity and correlating it with clinical findings. Results: Twenty-two patients showed positive CYP11B2 immunostaining in their tumors (aldosterone producing adenoma, APA). Four patients with CYP11B2-negative unilateral adenomas and 4 patients without tumors on computed tomography showed aldosterone-producing cell clusters (APCCs) with CYP11B2 immunostaining in the zona glomerulosa (multiple APCCs). The remaining 2 patients had unilateral multiple adrenocortical micronodules and diffuse adrenocortical hyperplasia, respectively. In APA, CYP11B2 score adjusted for tumor volume was positively correlated with plasma aldosterone and negatively correlated with serum potassium. The APA group was divided into 3 subgroups based on relative CYP11B2 and CYP11B1 immunostaining levels. The CYP11B2/CYP11B1-equivalent and CYP11B1-dominant APA groups showed significantly higher serum cortisol after 1 mg dexamethasone and larger tumor size than the CYP11B2-dominant APA group. Conclusions: The present study clearly demonstrates that CYP11B2 immunostaining is a powerful tool for histopathological diagnosis of aldosterone overproduction in PA and for subtype classification of APA, multiple APCCs, unilateral multiple adrenocortical micronodules, and diffuse hyperplasia.

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