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An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis

Background Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (... Full description

Journal Title: The lancet oncology 2009-08, Vol.10 (8), p.764-771
Main Author: van Nederveen, Francien H
Other Authors: Gaal, Jose , Favier, Judith , Korpershoek, Esther , Oldenburg, Rogier A , de Bruyn, Elly M. C. A , Sleddens, Hein F. B. M , Derkx, Pieter , Riviere, Julie , Dannenberg, Hilde , Petri, Bart-Jeroen , Komminoth, Paul , Pacak, Karel , Hop, Wim C. J , Pollard, Patrick J , Mannelli, Massimo , Bayley, Jean-Pierre , Perren, Aurel , Niemann, Stephan , Verhofstadt, Albert A , de Bruine, Aiaan P , Maher, Eamonn R , Tissier, Frederique , Meatchi, Tchao , Badoual, Cecile , Bertherat, Jerome , Amar, Laurence , Alataki, Despoina , Van Marck, Eric , Ferrau, Francesco , Francois, Jerney , de Herder, Wouter W , Peeters, Mark-Paul F. M. Vrancken , van Linge, Anne , Lenders, Jacques W. M , Gimenez-Roqueplo, Anne-Paule , de Krijgert, Ronald R , Dinjens, Winand N. M
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
ID: ISSN: 1470-2045
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title: An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis
format: Article
creator:
  • van Nederveen, Francien H
  • Gaal, Jose
  • Favier, Judith
  • Korpershoek, Esther
  • Oldenburg, Rogier A
  • de Bruyn, Elly M. C. A
  • Sleddens, Hein F. B. M
  • Derkx, Pieter
  • Riviere, Julie
  • Dannenberg, Hilde
  • Petri, Bart-Jeroen
  • Komminoth, Paul
  • Pacak, Karel
  • Hop, Wim C. J
  • Pollard, Patrick J
  • Mannelli, Massimo
  • Bayley, Jean-Pierre
  • Perren, Aurel
  • Niemann, Stephan
  • Verhofstadt, Albert A
  • de Bruine, Aiaan P
  • Maher, Eamonn R
  • Tissier, Frederique
  • Meatchi, Tchao
  • Badoual, Cecile
  • Bertherat, Jerome
  • Amar, Laurence
  • Alataki, Despoina
  • Van Marck, Eric
  • Ferrau, Francesco
  • Francois, Jerney
  • de Herder, Wouter W
  • Peeters, Mark-Paul F. M. Vrancken
  • van Linge, Anne
  • Lenders, Jacques W. M
  • Gimenez-Roqueplo, Anne-Paule
  • de Krijgert, Ronald R
  • Dinjens, Winand N. M
subjects:
  • COMPLEX-II
  • DISEASE
  • ENZYMATIC-ACTIVITY
  • FEATURES
  • HYPOXIA
  • LINE MUTATIONS
  • MALIGNANT PHEOCHROMOCYTOMAS
  • MITOCHONDRIAL RESPIRATORY-CHAIN
  • SUCCINATE
  • UPDATE
ispartof: The lancet oncology, 2009-08, Vol.10 (8), p.764-771
description: Background Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding The Netherlands Organisation for Scientific Research, Dutch Cancer Society Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1470-2045
fulltext: fulltext
issn:
  • 1470-2045
  • 1474-5488
url: Link


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titleAn immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis
sourceAlma/SFX Local Collection
creatorvan Nederveen, Francien H ; Gaal, Jose ; Favier, Judith ; Korpershoek, Esther ; Oldenburg, Rogier A ; de Bruyn, Elly M. C. A ; Sleddens, Hein F. B. M ; Derkx, Pieter ; Riviere, Julie ; Dannenberg, Hilde ; Petri, Bart-Jeroen ; Komminoth, Paul ; Pacak, Karel ; Hop, Wim C. J ; Pollard, Patrick J ; Mannelli, Massimo ; Bayley, Jean-Pierre ; Perren, Aurel ; Niemann, Stephan ; Verhofstadt, Albert A ; de Bruine, Aiaan P ; Maher, Eamonn R ; Tissier, Frederique ; Meatchi, Tchao ; Badoual, Cecile ; Bertherat, Jerome ; Amar, Laurence ; Alataki, Despoina ; Van Marck, Eric ; Ferrau, Francesco ; Francois, Jerney ; de Herder, Wouter W ; Peeters, Mark-Paul F. M. Vrancken ; van Linge, Anne ; Lenders, Jacques W. M ; Gimenez-Roqueplo, Anne-Paule ; de Krijgert, Ronald R ; Dinjens, Winand N. M
creatorcontribvan Nederveen, Francien H ; Gaal, Jose ; Favier, Judith ; Korpershoek, Esther ; Oldenburg, Rogier A ; de Bruyn, Elly M. C. A ; Sleddens, Hein F. B. M ; Derkx, Pieter ; Riviere, Julie ; Dannenberg, Hilde ; Petri, Bart-Jeroen ; Komminoth, Paul ; Pacak, Karel ; Hop, Wim C. J ; Pollard, Patrick J ; Mannelli, Massimo ; Bayley, Jean-Pierre ; Perren, Aurel ; Niemann, Stephan ; Verhofstadt, Albert A ; de Bruine, Aiaan P ; Maher, Eamonn R ; Tissier, Frederique ; Meatchi, Tchao ; Badoual, Cecile ; Bertherat, Jerome ; Amar, Laurence ; Alataki, Despoina ; Van Marck, Eric ; Ferrau, Francesco ; Francois, Jerney ; de Herder, Wouter W ; Peeters, Mark-Paul F. M. Vrancken ; van Linge, Anne ; Lenders, Jacques W. M ; Gimenez-Roqueplo, Anne-Paule ; de Krijgert, Ronald R ; Dinjens, Winand N. M
descriptionBackground Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding The Netherlands Organisation for Scientific Research, Dutch Cancer Society Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.
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subjectCOMPLEX-II ; DISEASE ; ENZYMATIC-ACTIVITY ; FEATURES ; HYPOXIA ; LINE MUTATIONS ; MALIGNANT PHEOCHROMOCYTOMAS ; MITOCHONDRIAL RESPIRATORY-CHAIN ; SUCCINATE ; UPDATE
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0van Nederveen, Francien H
1Gaal, Jose
2Favier, Judith
3Korpershoek, Esther
4Oldenburg, Rogier A
5de Bruyn, Elly M. C. A
6Sleddens, Hein F. B. M
7Derkx, Pieter
8Riviere, Julie
9Dannenberg, Hilde
10Petri, Bart-Jeroen
11Komminoth, Paul
12Pacak, Karel
13Hop, Wim C. J
14Pollard, Patrick J
15Mannelli, Massimo
16Bayley, Jean-Pierre
17Perren, Aurel
18Niemann, Stephan
19Verhofstadt, Albert A
20de Bruine, Aiaan P
21Maher, Eamonn R
22Tissier, Frederique
23Meatchi, Tchao
24Badoual, Cecile
25Bertherat, Jerome
26Amar, Laurence
27Alataki, Despoina
28Van Marck, Eric
29Ferrau, Francesco
30Francois, Jerney
31de Herder, Wouter W
32Peeters, Mark-Paul F. M. Vrancken
33van Linge, Anne
34Lenders, Jacques W. M
35Gimenez-Roqueplo, Anne-Paule
36de Krijgert, Ronald R
37Dinjens, Winand N. M
title
0An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis
1The lancet oncology
descriptionBackground Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding The Netherlands Organisation for Scientific Research, Dutch Cancer Society Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.
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0van Nederveen, Francien H
1Gaal, Jose
2Favier, Judith
3Korpershoek, Esther
4Oldenburg, Rogier A
5de Bruyn, Elly M. C. A
6Sleddens, Hein F. B. M
7Derkx, Pieter
8Riviere, Julie
9Dannenberg, Hilde
10Petri, Bart-Jeroen
11Komminoth, Paul
12Pacak, Karel
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14Pollard, Patrick J
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16Bayley, Jean-Pierre
17Perren, Aurel
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20de Bruine, Aiaan P
21Maher, Eamonn R
22Tissier, Frederique
23Meatchi, Tchao
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25Bertherat, Jerome
26Amar, Laurence
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29Ferrau, Francesco
30Francois, Jerney
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32Peeters, Mark-Paul F. M. Vrancken
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35Gimenez-Roqueplo, Anne-Paule
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titleAn immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis
authorvan Nederveen, Francien H ; Gaal, Jose ; Favier, Judith ; Korpershoek, Esther ; Oldenburg, Rogier A ; de Bruyn, Elly M. C. A ; Sleddens, Hein F. B. M ; Derkx, Pieter ; Riviere, Julie ; Dannenberg, Hilde ; Petri, Bart-Jeroen ; Komminoth, Paul ; Pacak, Karel ; Hop, Wim C. J ; Pollard, Patrick J ; Mannelli, Massimo ; Bayley, Jean-Pierre ; Perren, Aurel ; Niemann, Stephan ; Verhofstadt, Albert A ; de Bruine, Aiaan P ; Maher, Eamonn R ; Tissier, Frederique ; Meatchi, Tchao ; Badoual, Cecile ; Bertherat, Jerome ; Amar, Laurence ; Alataki, Despoina ; Van Marck, Eric ; Ferrau, Francesco ; Francois, Jerney ; de Herder, Wouter W ; Peeters, Mark-Paul F. M. Vrancken ; van Linge, Anne ; Lenders, Jacques W. M ; Gimenez-Roqueplo, Anne-Paule ; de Krijgert, Ronald R ; Dinjens, Winand N. M
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32Peeters, Mark-Paul F. M. Vrancken
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6Sleddens, Hein F. B. M
7Derkx, Pieter
8Riviere, Julie
9Dannenberg, Hilde
10Petri, Bart-Jeroen
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29Ferrau, Francesco
30Francois, Jerney
31de Herder, Wouter W
32Peeters, Mark-Paul F. M. Vrancken
33van Linge, Anne
34Lenders, Jacques W. M
35Gimenez-Roqueplo, Anne-Paule
36de Krijgert, Ronald R
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atitleAn immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis
jtitleThe lancet oncology
date2009-08
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pages764-771
issn1470-2045
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abstractBackground Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding The Netherlands Organisation for Scientific Research, Dutch Cancer Society Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.