TY - JOUR
T1 - SDHD immunohistochemistry
T2 - A new tool to validate SDHx mutations in pheochromocytoma/paraganglioma
AU - Menara, Mélanie
AU - Oudijk, Lindsey
AU - Badoual, Cécile
AU - Bertherat, Jérôme
AU - Lepoutre-Lussey, Charlotte
AU - Amar, Laurence
AU - Iturrioz, Xavier
AU - Sibony, Mathilde
AU - Zinzindohoué, Frank
AU - De Krijger, Ronald
AU - Gimenez-Roqueplo, Anne Paule
AU - Favier, Judith
N1 - Publisher Copyright:
Copyright © 2015 by the Endocrine Society.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Context: Pheochromocytomas (PCC) and paragangliomas (PGL) may be caused by a germline mutation in 12 different predisposing genes. We previously reported that immunohistochemistry is a useful approach to detect patients harboring SDHx mutations. SDHA immunostaining is negative in SDHA-mutated tumors only, while SDHB immunostaining is negative in samples mutated on all SDHx genes. In some cases of SDHD or SDHC-mutated tumors, a weak diffuse SDHB labeling has however been described. Objective: Here, we addressed whether the same procedure could be applicable to detect patients with germline SDHD mutations, by testing two new commercially available anti-SDHD antibodies. Design and Methods: We performed a retrospective study on 170 PGL/PCC in which we investigated SDHD and SDHB expression by immunohistochemistry. Results: SDHx-mutated PGL/PCC showed a completely negative SDHB staining (23/27) or a weak cytoplasmic background (4/27). Unexpectedly, weobserved that SDHD immunohistochemistry was positive in SDHx-deficient tumors and negative in the other samples. Twenty-six of 27 SDHx tumors (including the four weakly stained for SDHB) were positive for SDHD. Among non-SDHx tumors, 138/143 were positive for SDHB and negative for SDHD. Five cases showed a negative immuno-staining for SDHB, but were negative for SDHD. Conclusion: Our results demonstrate that a positive SDHD immunostaining predicts the presence of an SDHx gene mutation. Because SDHB negative immunostaining is sometimes difficult to interpret in the case of background, the addition of SDHD positive immunohistochemistry will be a very useful tool to predict or validate SDHx gene variants in PGL/PCC.
AB - Context: Pheochromocytomas (PCC) and paragangliomas (PGL) may be caused by a germline mutation in 12 different predisposing genes. We previously reported that immunohistochemistry is a useful approach to detect patients harboring SDHx mutations. SDHA immunostaining is negative in SDHA-mutated tumors only, while SDHB immunostaining is negative in samples mutated on all SDHx genes. In some cases of SDHD or SDHC-mutated tumors, a weak diffuse SDHB labeling has however been described. Objective: Here, we addressed whether the same procedure could be applicable to detect patients with germline SDHD mutations, by testing two new commercially available anti-SDHD antibodies. Design and Methods: We performed a retrospective study on 170 PGL/PCC in which we investigated SDHD and SDHB expression by immunohistochemistry. Results: SDHx-mutated PGL/PCC showed a completely negative SDHB staining (23/27) or a weak cytoplasmic background (4/27). Unexpectedly, weobserved that SDHD immunohistochemistry was positive in SDHx-deficient tumors and negative in the other samples. Twenty-six of 27 SDHx tumors (including the four weakly stained for SDHB) were positive for SDHD. Among non-SDHx tumors, 138/143 were positive for SDHB and negative for SDHD. Five cases showed a negative immuno-staining for SDHB, but were negative for SDHD. Conclusion: Our results demonstrate that a positive SDHD immunostaining predicts the presence of an SDHx gene mutation. Because SDHB negative immunostaining is sometimes difficult to interpret in the case of background, the addition of SDHD positive immunohistochemistry will be a very useful tool to predict or validate SDHx gene variants in PGL/PCC.
UR - http://www.scopus.com/inward/record.url?scp=84927566098&partnerID=8YFLogxK
U2 - 10.1210/jc.2014-1870
DO - 10.1210/jc.2014-1870
M3 - Article
C2 - 25405498
AN - SCOPUS:84927566098
SN - 0021-972X
VL - 100
SP - E287-E291
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -