SDHA Immunohistochemistry Detects Germline SDHA Gene Mutations in Apparently Sporadic Paragangliomas and Pheochromocytomas

Context: Pheochromocytoma- paragangliomasyndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase(SDH), and in SDHAF2, required for flavination of SDHA. A recent report described a patient with an abdominal paraganglioma, immunohistochemically negative for SDHA, and identified a causal germline mutationin SDHA. Objective: In this study, we evaluated the significance of SDHAimmunohistochemistry in the identification of new patients with SDHAmutations. Setting: This study was performed in the ErasmusMedical Center in Rotterdam (The Netherlands) and the Universite Paris Descartes in Paris (France). Methods: We investigated 316 pheochromocytomasand paragangliomasfor SDHAexpression. Sequence analysis of SDHAwas performed on all tumors that were immunohistochemically negative for SDHAand on a subset of tumors immunohistochemically positive for SDHA. Results: Six tumors were immunohistochemically negative for SDHA. Four tumors from Dutch patients showed a ger...