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Immunohistochemical expression of CYP11A1, CYP11B, CYP17, and HSD3B2 in functional and nonfunctional canine adrenocortical tumors

Allan, F; Watson, AH; Syme, HM

Authors

F Allan

AH Watson

HM Syme



Abstract

Background: Functionality of human adrenal tumors is inferred by CYP11B1 (cortisol synthase) expression, CYP11B2 (aldosterone synthase) expression, or both. Hypothesis/Objectives: Nonfunctional canine adrenal tumors have low expression of steroidogenic enzymes, whereas aldosterone-producing tumors express CYP11B, and cortisol-producing tumors express both CYP11B and CYP17. AnimalsTwenty-two client-owned dogs with adrenocortical tumors (ACT) (8 nonfunctional, 7-cortisol producing, 2 aldosterone-producing and 5 functional noncortisol producing) and 2 dogs with normal adrenal glands. Methods: Retrospective case series. Adrenal functionality was determined from clinical signs and endocrine testing. CYP11A1, CYP11B, CYP17, and HSD3B2 expression was detected by immunohistochemistry on formalin-fixed paraffin-embedded adrenal tissue. Protein expression was semiquantified by 2 blinded observers using H-scoring (results reported as median [range]) and compared in nonfunctional and cortisol-producing adrenal tumors by Mann-Whitney U tests. Results: CYP11A1, CYP11B, and HSD3B2 were present within all cortical layers of normal adrenal glands, and CYP17 was expressed within the zona fasciculata and zona reticularis. Expression of CYP11A1 (191.25 [97.5-270] vs. 175 [102.5-295] P = .69), CYP11B (190 [130-265] vs. 147.5 [95-202.5]; P = .07), CYP17 (177.5 [87.5-240] vs. 247.5 [55-292.5]; P = .40), and HSD3B2 (230 [47.5-295] vs. 277.5 [67.5-295]; P = .34) were not significantly different between cortisol-producing and nonfunctional ACT. Conclusions and Clinical Importance: Our findings suggest it is not possible to determine functionality of canine ACT by immunohistochemistry for steroidogenic enzymes. Tumor size cannot be used to infer functionality of adrenal tumors.

Citation

Allan, F., Watson, A., & Syme, H. (2024). Immunohistochemical expression of CYP11A1, CYP11B, CYP17, and HSD3B2 in functional and nonfunctional canine adrenocortical tumors. Journal of Veterinary Internal Medicine, https://doi.org/10.1111/jvim.17212

Journal Article Type Article
Acceptance Date Sep 25, 2024
Online Publication Date Oct 10, 2024
Publication Date 2024
Deposit Date Oct 28, 2024
Publicly Available Date Oct 28, 2024
Print ISSN 0891-6640
Electronic ISSN 1939-1676
Publisher Wiley Open Access
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1111/jvim.17212
Keywords adrenocortical neoplasia; hyperadrenocorticism; hyperaldosteronism; immunohistochemistry; steroidogenic enzyme; STEROIDOGENIC ENZYMES; CONSENSUS; RECEPTOR; DOGS

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