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Σάββατο 15 Δεκεμβρίου 2018

Clinical significance and peculiarities of succinate dehydrogenase B and hypoxia inducible factor 1α expression in parasympathetic versus sympathetic paragangliomas

Abstract

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‐1α (HIF‐1α) as a biomarker for succinate dehydrogenase (SDHx)‐mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF‐1α proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers.

Methods

The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF‐1α 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‐1α stabilization was associated with SDHx‐mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx‐HNPGLs lacked HIF‐1α 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‐1α stabilization in HNPGLs, this is not a clinically useful biomarker.



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