SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas

Esther Korpershoek, Judith Favier, José Gaal, Nelly Burnichon, Bram Van Gessel, Lindsey Oudijk, Cećile Badoual, Noeḿie Gadessaud, Annabelle Venisse, Jean Pierre Bayley, Marieke F. Van Dooren, Wouter W. De Herder, Fred́eŕique Tissier, Pierre Franco̧is Plouin, Francien H. Van Nederveen, Winand N.M. Dinjens, Anne Paule Gimenez-Roqueplo, Ronald R. De Krijger

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

252 Citaten (Scopus)


Context: 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. Objective: In this study, we evaluated the significance of SDHA immunohistochemistry in the identification of new patients with SDHA mutations. Setting: This study was performed in the Erasmus Medical Center in Rotterdam (The Netherlands) and the Université Paris Descartes in Paris (France). Methods: 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. Results: 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 wildtype SDHA allele was confirmed by loss of heterozygosity analysis. Sequence analysis of 35 SDHA immunohistochemically positive tumors did not reveal additional SDHA mutations. Conclusions: 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.

Originele taal-2Engels
Pagina's (van-tot)E1472-E1476
TijdschriftJournal of Clinical Endocrinology and Metabolism
Nummer van het tijdschrift9
StatusGepubliceerd - sep. 2011
Extern gepubliceerdJa


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