Watson Alice, Allan Frederik, Harrington Norelene, Mahony Orla, Brown Morris, Syme Harriet
Royal Veterinary College, London, UK.
Queen Mary University of London, London, UK.
Vet Pathol. 2025 Sep;62(5):672-682. doi: 10.1177/03009858251331146. Epub 2025 Apr 21.
It is suggested that primary hyperaldosteronism (PHA) is an under-diagnosed cause of systemic hypertension in cats. No immunohistochemical markers of aldosterone synthesizing tissues have been identified, meaning that endocrine function cannot be inferred from examining feline tissues. In humans, expression of CYP11B2 (aldosterone synthase) is used for this purpose, but cats have a single CYP11B enzyme responsible for the terminal steps in synthesis of both aldosterone and cortisol, precluding its use as an indicator of steroidogenic function. This study aimed to identify immunohistochemical markers of aldosterone producing tissues. In addition, since there are no existing guidelines for classification of feline adrenal tumors as benign or malignant, this study aimed to investigate potential markers of adrenal tumor malignancy in PHA. Normal adrenals ( = 9) and adrenal tumors secreting aldosterone ( = 31) or cortisol ( = 4) were immunolabeled for steroidogenic enzymes (CYP11B, CYP17A1, and CYB5A), the zona glomerulosa (including KCNJ5 visinin-like 1 (VSNL1), and neuron-specific enolase (NSE)), and proliferation markers (Ki67). Histochemical staining for reticulin was also performed. Transcriptomes of normal ( = 4) and aldosterone secreting tumors ( = 5) were compared. Weak or absent CYP17A1 in conjunction with strong KCNJ5 or VSNL1 immunolabeling was present in aldosterone producing tissues from normal and tumorous cat adrenals. RNA expression was lower in aldosterone producing tumors compared with normal adrenals ( < .0001). VSNL1 and NSE were not specific markers of aldosterone producing tissue. CYB5A and CYP17A1 were not expressed within the zona reticularis, suggesting minimal adrenal production of androgens. Ki67 proliferative index and reticulin network disruption were not predictive of malignancy.
有研究表明，原发性醛固酮增多症（PHA）是猫全身性高血压的一个诊断不足的病因。目前尚未发现醛固酮合成组织的免疫组化标志物，这意味着无法通过检查猫组织来推断内分泌功能。在人类中，CYP11B2（醛固酮合酶）的表达用于此目的，但猫有一种单一的CYP11B酶负责醛固酮和皮质醇合成的终末步骤，因此不能将其用作类固醇生成功能的指标。本研究旨在确定产生醛固酮组织的免疫组化标志物。此外，由于目前尚无将猫肾上腺肿瘤分类为良性或恶性的指南，本研究旨在调查PHA中肾上腺肿瘤恶性程度的潜在标志物。对正常肾上腺（n = 9）以及分泌醛固酮（n = 31）或皮质醇（n = 4）的肾上腺肿瘤进行免疫标记，检测类固醇生成酶（CYP11B、CYP17A1和CYB5A）、球状带（包括KCNJ5视紫质样蛋白1（VSNL1）和神经元特异性烯醇化酶（NSE））以及增殖标志物（Ki67）。还进行了网状纤维的组织化学染色。比较了正常肾上腺（n = 4）和分泌醛固酮肿瘤（n = 5）的转录组。正常和肿瘤性猫肾上腺产生醛固酮的组织中，CYP17A1表达较弱或缺失，同时KCNJ5或VSNL1免疫标记较强。与正常肾上腺相比，产生醛固酮的肿瘤中RNA表达较低（P <.0001）。VSNL1和NSE不是产生醛固酮组织的特异性标志物。CYB5A和CYP17A1在网状带中未表达，提示肾上腺雄激素生成极少。Ki67增殖指数和网状纤维网络破坏不能预测恶性程度。
