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

Authors :
Gill AJ
Benn DE
Chou A
Clarkson A
Muljono A
Meyer-Rochow GY
Richardson AL
Sidhu SB
Robinson BG
Clifton-Bligh RJ
Source :
Human pathology [Hum Pathol] 2010 Jun; Vol. 41 (6), pp. 805-14. Date of Electronic Publication: 2010 Mar 17.
Publication Year :
2010

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.<br /> (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1532-8392
Volume :
41
Issue :
6
Database :
MEDLINE
Journal :
Human pathology
Publication Type :
Academic Journal
Accession number :
20236688
Full Text :
https://doi.org/10.1016/j.humpath.2009.12.005