Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes.

Show simple item record Gill, AJ en Benn, DE en Chou, A en Clarkson, A en Muljono, A en Meyer-Rochow, Goswin en Richardson, AL en Sidhu, SB en Robinson, BG en Clifton-Bligh, RJ en
dc.coverage.spatial United States en 2012-05-30T03:29:07Z en 2010-06 en
dc.identifier.citation Human Pathology 41(6):805-814 Jun 2010 en
dc.identifier.uri en
dc.description.abstract Up to 30% of pheochromocytomas and paragangliomas are associated with germline RET, Von Hippel-Lindau (VHL), neurofibromatosis type I (NF1), and succinate dehydrogenase subunits (SDHB, SDHC, and SDHD) mutations. Genetic testing allows familial counseling and identifies subjects at high risk of malignancy (SDHB mutations) or significant multiorgan disease (RET, VHL, or NF1). However, conventional genetic testing for all loci is burdensome and costly. We performed immunohistochemistry for SDHB on 58 tumors with known SDH mutation status. We defined positive as granular cytoplasmic staining (a mitochondrial pattern), weak diffuse as a cytoplasmic blush lacking definite granularity, and negative as completely absent staining in the presence of an internal positive control. All 12 SDH mutated tumors (6 SDHB, 5 SDHD, and 1 SDHC) showed weak diffuse or negative staining. Nine of 10 tumors with known mutations of VHL, RET, or NF1 showed positive staining. One VHL associated tumor showed weak diffuse staining. Of 36 tumors without germline mutations, 34 showed positive staining. One paraganglioma with no known SDH mutation but clinical features suggesting familial disease was negative, and one showed weak diffuse staining. We also performed immunohistochemistry for SDHB on 143 consecutive unselected tumors of which 21 were weak diffuse or negative. As SDH mutations are virtually always germline, we conclude that approximately 15% of all pheochromocytomas or paragangliomas are associated with germline SDH mutation and that immunohistochemistry can be used to triage genetic testing. Completely absent staining is more commonly found with SDHB mutation, whereas weak diffuse staining often occurs with SDHD mutation. en
dc.language eng en
dc.publisher Elsevier en
dc.relation.ispartofseries Human Pathology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.subject Adrenal Gland Neoplasms en
dc.subject Adult en
dc.subject Aged en
dc.subject Cohort Studies en
dc.subject Female en
dc.subject Genetic Testing en
dc.subject Germ-Line Mutation en
dc.subject Humans en
dc.subject Immunohistochemistry en
dc.subject Male en
dc.subject Membrane Proteins en
dc.subject Middle Aged en
dc.subject Paraganglioma en
dc.subject Pheochromocytoma en
dc.subject Succinate Dehydrogenase en
dc.subject Syndrome en
dc.subject Young Adult en
dc.title Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.humpath.2009.12.005 en
pubs.issue 6 en
pubs.begin-page 805 en
pubs.volume 41 en
dc.rights.holder Copyright: Elsevier en
dc.identifier.pmid 20236688 en
pubs.end-page 814 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 175470 en Medical and Health Sciences en School of Medicine en Surgery Department en
dc.identifier.eissn 1532-8392 en
dc.identifier.pii S0046-8177(09)00456-0 en
pubs.record-created-at-source-date 2012-05-30 en
pubs.dimensions-id 20236688 en

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