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

2011; Oxford University Press; Volume: 96; Issue: 9 Linguagem: Inglês

10.1210/jc.2011-1043

1945-7197

Esther Korpershoek, Judith Favier, José Gaal, Nelly Burnichon, Bram van Gessel, Lindsey Oudijk, Cécile Badoual, Noémie Gadessaud, Annabelle Vénisse, Jean‐Pierre Bayley, Marieke F. van Dooren, Wouter W. de Herder, Frédérique Tissier, Pierre‐François Plouin, Francien H. van Nederveen, Winand N.M. Dinjens, Anne‐Paule Gimenez‐Roqueplo, Ronald R. de Krijger,

Hormonal Regulation and Hypertension

Pheochromocytoma-paraganglioma syndrome 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 mutation in SDHA.In this study, we evaluated the significance of SDHA immunohistochemistry in the identification of new patients with SDHA mutations.This study was performed in the Erasmus Medical Center in Rotterdam (The Netherlands) and the Université Paris Descartes in Paris (France).We investigated 316 pheochromocytomas and paragangliomas for SDHA expression. Sequence analysis of SDHA was performed on all tumors that were immunohistochemically negative for SDHA and on a subset of tumors immunohistochemically positive for SDHA.Six tumors were immunohistochemically negative for SDHA. Four tumors from Dutch patients showed a germline c.91C → T SDHA gene mutation (p.Arg31X). Another tumor (from France) carried a germline SDHA missense mutation c.1753C → T (p.Arg585Trp). Loss of the wild-type SDHA allele was confirmed by loss of heterozygosity analysis. Sequence analysis of 35 SDHA immunohistochemically positive tumors did not reveal additional SDHA mutations.Our results demonstrate that SDHA immunohistochemistry on paraffin-embedded tumors can reveal the presence of SDHA germline mutations and allowed the identification of SDHA-related tumors in at least 3% of patients affected by apparently sporadic (para)sympathetic paragangliomas and pheochromocytomas.