SDHB and SDHA Immunohistochemistry in Canine Pheochromocytomas

Firas M Abed,Melissa A Brown,Omar A Al-Mahmood,Michael J Dark

doi:10.3390/ani10091683

Firas M Abed, Melissa A Brown + Show 2 more

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https://doi.org/10.3390/ani10091683

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Abstract

Simple SummaryPheochromocytomas are adrenal tumors that occur in both dogs and people. One of the more common gene families involved in the development of this tumor in people is succinate dehydrogenase (SDH). In people, immunohistochemistry can be used with biopsy samples to predict gene pathways that may be involved in the development of the tumor. This is faster and cheaper than performing extensive sequencing to determine if genes are involved. We tested 35 dog tumors to determine how likely SDH mutations were. While our data suggest significant numbers of SDH mutations, these mutations do not appear to be associated with tumor aggression.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.

Highlights

Pheochromocytomas (PCs) are catecholamine-secreting neuroendocrine tumors arising from the chromaffin cells of the neural crest [1,2,3]
We examined the expression of succinate dehydrogenase A (SDHA) and succinate dehydrogenase B (SDHB) in canine pheochromocytomas and compared these with data on patient age, tumor size, and invasion, in order to determine the utility of succinate dehydrogenase (SDH) IHC in canine pheochromocytoma diagnostics
All 40 controls had an intracytoplasmic immunoreactivity for SDHA and SDHB similar to that found in human tissues (Figure 1A,B)

Summary

Introduction

Pheochromocytomas (PCs) are catecholamine-secreting neuroendocrine tumors arising from the chromaffin cells of the neural crest [1,2,3]. While canine pheochromocytomas are usually benign, they can invade adjacent tissues and may be malignant, with metastasis to distant tissues [4]. Immunohistochemistry (IHC) data has found that canine and human PCs are highly similar, as neoplastic cells in both share the expression of numerous antigens, including S100, synaptophysin (SYN), chromogranin A (CGA), and substance P (SP) [7]. Known genetic mutations are involved in the pathogenesis of approximately 60% of human PCs. Known genetic mutations are involved in the pathogenesis of approximately 60% of human PCs These are associated with mutations in the succinate dehydrogenase (SDH) family of genes, with mutations in succinate dehydrogenase subunit B (SDHB) associated with a high likelihood of metastasis/malignancy [5]. The sequencing of multiple SDH genes in every pheochromocytoma is economically infeasible in veterinary medicine, making the determination of the genetic basis of PC in dogs uncertain

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