H-score of 11β-hydroxylase and aldosterone synthase in the histopathological diagnosis of adrenocortical tumors
- 77 Downloads
To assess the diagnostic performance of the H-score of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) in the histopathological diagnosis of adrenocortical tumors (ACT).
We retrospectively evaluated 199 cases of ACT, of which 85 were diagnosed as aldosterone-producing adenoma (APA), 66 as cortisol-producing adenoma (CPA), 9 as aldosterone–cortisol co-secreting adenoma, 30 as nonhyperfunctioning adenoma, and 9 as adrenocortical carcinoma (ACC). Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies. The staining was quantified by the McCarty’s H-score system. The diagnostic performance was assessed by the receiver operating characteristic curve (ROC).
The H-score of CYP11B1 is highest in the CPA group and lowest in the ACC group. The H-score of CYP11B2 in the APA group is significantly higher than other ACT groups. The area under ROC (AUC) of an increased H-score of CYP11B2 (>65) for the diagnosis of APA was 0.971 (95%CI 0.937–0.990). The AUC of an increased H-score of CYP11B1 (>204) for the diagnosis of CPA was 0.725 (95%CI 0.658–0.786). The AUC of a decreased H-score of CYP11B1 (<85) for the diagnosis of ACC was 0.960 (95%CI 0.923–0.983).
H-score of CYP11B1 and CYP11B2 are reliable tools for the histopathological subtyping of functional benign ACT and may offer some value in the histopathological diagnosis of malignant ACT.
KeywordsAdrenocortical Tumors 11β-hydroxylase Aldosterone synthase H-score Histopathological diagnosis
The authors thank Laboratory of Endocrine and Laboratory of Lipid & Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University. The authors also thank Chuan Peng, Rufei Gao, and Xiaoqiu Xiao (from Laboratory of Lipid & Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University) for suggestions of study design and revision.
This study was funded by National Key Clinical Specialties Construction Program of China to the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University; and the National Natural Science Foundation of China (81670785) to Q.L.; and the National Natural Science Foundation of China (81800701) to Y.S.; and the Fundamental Science & Advanced Technology Research of Chongqing (Major Project, cstc2015jcyjBX0096) to Q.L.; and Chongqing Science and Technology Committee Innovation Project (Technology Development and Application of Precision Medicine, cstc2016shms-ztzx1003) to Q.L.; and the Joint Medical Research Project of Chongqing Science and Technology Commission and Chongqing Health and Family Planning Commission (Youth Project, 2018QNXM001) to J.H.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
A written informed consent was obtained from each participant enrolled.
- 4.S. Monticone, F. D’Ascenzo, C. Moretti, T.A. Williams, F. Veglio, F. Gaita, P. Mulatero, Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 6(1), 41–50 (2018)CrossRefGoogle Scholar
- 11.E. Mornet, J. Dupont, A. Vitek, P.C. White, Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). J. Biol. Chem. 264(35), 20961–20967 (1989)Google Scholar
- 12.T. Ogishima, H. Shibata, H. Shimada, F. Mitani, H. Suzuki, T. Saruta, Y. Ishimura, Aldosterone synthase cytochrome P-450 expressed in the adrenals of patients with primary aldosteronism. J. Biol. Chem. 266(17), 10731–10734 (1991)Google Scholar
- 15.F. Kubota-Nakayama, Y. Nakamura, S. Konosu-Fukaya, A. Azmahani, K. Ise, Y. Yamazaki, Y. Kitawaki, S.J. Felizola, Y. Ono, K. Omata et al. Expression of steroidogenic enzymes and their transcription factors in cortisol-producing adrenocortical adenomas: immunohistochemical analysis and quantitative real-time polymerase chain reaction studies. Hum. Pathol. 54, 165–173 (2016)CrossRefGoogle Scholar
- 16.T. Dekkers, M. ter Meer, J.W. Lenders, A.R. Hermus, L. Schultze Kool, J.F. Langenhuijsen, K. Nishimoto, T. Ogishima, K. Mukai, E.A. Azizan et al. Adrenal nodularity and somatic mutations in primary aldosteronism: one node is the culprit? J. Clin. Endocrinol. Metab. 99(7), E1341–E1351 (2014)CrossRefGoogle Scholar
- 19.J.W. Funder, R.M. Carey, F. Mantero, M.H. Murad, M. Reincke, H. Shibata, M. Stowasser, W.F. Young Jr, The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 101(5), 1889–1916 (2016)CrossRefGoogle Scholar
- 20.T.A. Williams, J.W.M. Lenders, P. Mulatero, J. Burrello, M. Rottenkolber, C. Adolf, F. Satoh, L. Amar, M. Quinkler, J. Deinum et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 5(9), 689–699 (2017)CrossRefGoogle Scholar
- 25.D.A. Budwit-Novotny, K.S. McCarty, E.B. Cox, J.T. Soper, D.G. Mutch, W.T. Creasman, J.L. Flowers, K.S. McCarty Jr, Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 46(10), 5419–5425 (1986)Google Scholar
- 26.K. Nishimoto, M. Koga, T. Seki, K. Oki, E.P. Gomez-Sanchez, C.E. Gomez-Sanchez, M. Naruse, T. Sakaguchi, S. Morita, T. Kosaka et al. Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. Mol. Cell Endocrinol. 441, 124–133 (2017)CrossRefGoogle Scholar
- 30.Y. Ono, Y. Nakamura, T. Maekawa, S.J. Felizola, R. Morimoto, Y. Iwakura, M. Kudo, K. Seiji, K. Takase, Y. Arai et al. Different expression of 11beta-hydroxylase and aldosterone synthase between aldosterone-producing microadenomas and macroadenomas. Hypertension 64(2), 438–444 (2014)CrossRefGoogle Scholar