Clinical Significance And Peculiarities Of Succinate Dehydrogenase B And Hypoxia Inducible Factor 1 Alpha Expression In Parasympathetic Versus Sympathetic Paragangliomas

Background Succinate dehydrogenase subunit B (SDHB) immunohistochemistry was considered a valuable tool to identify patients with inherited paraganglioma/pheochromocytoma (PGL/PCC). However, previous studies jointly analyzed 2 related but clinically distinct entities, parasympathetic head and neck paragangliomas (HNPGLs) and sympathetic PCCs/PGLs. Additionally, a role for hypoxia inducible factor-1 alpha (HIF-1 alpha) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1 alpha proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. Methods The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1 alpha immunohistochemistry analysis was performed in 158 genetically defined patients. Results Similarly to PCCs/PGLs, SDHB immune-negativity correlated with SDHx-mutations in HNPGLs (P < .0001). The HIF-1 alpha stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1 alpha positive cells. Conclusion As in PCCs/PGLs, SDHB immunohistochemistry in HNPGLs is a valuable method for identification of candidates for SDHx-genetic testing. On the contrary, although SDHx mutations may favor HIF-1 alpha stabilization in HNPGLs, this is not a clinically useful biomarker.