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The Value of 11β-Hydroxylase and Aldosterone Synthase-Based H-Score in the Pathological Diagnosis of Adrenocortical Tumors
22 Pages Posted: 13 Sep 2018
More...Abstract
Summary Background: Immunohistochemical staining is important for the pathological diagnosis of adrenocortical tumors (ACT), while the biomarker is lacking. 11β-Hydroxylase (CYP11B1) and Aldosterone Synthase (CYP11B2) are crucial for the cortisol and aldosterone synthesis. We aimed to assess the diagnostic performance of the H-score of CYP11B1 and CYP11B2 immunoreactivity among ACT.
Methods: We retrospectively evaluated 203 cases of ACT, of which 85 were diagnosed as aldosterone producing adenoma (APA), 66 as cortisol producing adenoma (CPA), 30 as non-hyperfunctioning adenoma (NHFA), 12 as adrenal myelolipoma (AML), 6 as adrenal cortical carcinoma (ACC) and 4 as primary bilateral macronodular hyperplasia (PBMAH). Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies. The staining was quantified by McCarty's H-score system. The diagnostic performance was assessed by the receiver operating characteristic curve (ROC).
Findings: The H-score of CYP11B1 is lowest in the ACC group and highest in the CPA group. The H-score of CYP11B2 in the APA group is significantly higher than other ACT groups. The area under ROC (AUC) of a decreased CYP11B1 H-score (<85) for established ACC was 0.963 (95% CI, 0.517 to 0.651). The AUC of an increased CYP11B1 H-score (>180) for CPA was 0.732 (0.666-0.792). The AUC of an increased CYP11B2 H-score (>85) for APA was 0.971 (0.939-0.989). Further sub-group analyses showed similar results.
Interpretation: The H-scores of CYP11B1 and CYP11B2 are reliable tools for the pathological diagnosis of ACT. A decreased CYP11B1 H-score suggests a possibility of ACC, and an increased H-score of CYP11B1 gives a clue of CPA. An increased CYP11B2 H-score is sufficient for the APA diagnosis.
Funding: National Key Clinical Specialties Construction Program of China; and the National Natural Science Foundation of China (81670785); and the Fundamental Science & Advanced Technology Research of Chongqing (Major Project, cstc2015jcyjBX0096): Chongqing Science and Technology Committee Innovation Project (Technology Development and Application of Precision Medicine, cstc2016shms-ztzx1003).
Declaration of Interest: Authors have disclosed no conflicts of interest.
Ethical Approval: This study was approved by the ethics committee of the first affiliated hospital of Chongqing medical university and an informed written consent was obtained from each participant.
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