Abed Firas M, Brown Melissa A, Al-Mahmood Omar A, Dark Michael J
Department of Comparative, Diagnostic and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Veterinary Diagnostic Laboratories, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Animals (Basel). 2020 Sep 17;10(9):1683. doi: 10.3390/ani10091683.
Pheochromocytomas (PCs) are tumors arising from the chromaffin cells of the adrenal glands and are the most common tumors of the adrenal medulla in animals. In people, these are highly correlated to inherited gene mutations in the succinate dehydrogenase (SDH) pathway; however, to date, little work has been done on the genetic basis of these tumors in animals. In humans, immunohistochemistry has proven valuable as a screening technique for SDH mutations. Human PCs that lack succinate dehydrogenase B (SDHB) immunoreactivity have a high rate of mutation in the SDH family of genes, while human PCs lacking succinate dehydrogenase A (SDHA) immunoreactivity have mutations in the SDHA gene. To determine if these results are similar for dogs, we performed SDHA and SDHB immunohistochemistry on 35 canine formalin-fixed, paraffin-embedded (FFPE) PCs. Interestingly, there was a loss of immunoreactivity for both SDHA and SDHB in four samples (11%), suggesting a mutation in SDHx including SDHA. An additional 25 (71%) lacked immunoreactivity for SDHB, while retaining SDHA immunoreactivity. These data suggest that 29 out of the 35 (82%) may have an SDH family mutation other than SDHA. Further work is needed to determine if canine SDH immunohistochemistry on PCs correlates to genetic mutations that are similar to human PCs.
嗜铬细胞瘤（PCs）是起源于肾上腺嗜铬细胞的肿瘤，是动物肾上腺髓质最常见的肿瘤。在人类中，这些肿瘤与琥珀酸脱氢酶（SDH）途径中的遗传性基因突变高度相关；然而，迄今为止，关于这些肿瘤在动物中的遗传基础的研究很少。在人类中，免疫组织化学已被证明是一种筛选SDH突变的有价值的技术。缺乏琥珀酸脱氢酶B（SDHB）免疫反应性的人类PCs在SDH基因家族中有很高的突变率，而缺乏琥珀酸脱氢酶A（SDHA）免疫反应性的人类PCs在SDHA基因中有突变。为了确定这些结果在犬类中是否相似，我们对35例犬类福尔马林固定、石蜡包埋（FFPE）的PCs进行了SDHA和SDHB免疫组织化学检测。有趣的是，在四个样本（11%）中SDHA和SDHB均失去了免疫反应性，提示包括SDHA在内的SDHx发生了突变。另外25个样本（71%）缺乏SDHB免疫反应性，同时保留SDHA免疫反应性。这些数据表明，35个样本中有29个（82%）可能存在除SDHA之外的SDH家族突变。需要进一步研究来确定犬类PCs的SDH免疫组织化学是否与类似于人类PCs的基因突变相关。
