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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
- Source :
- Lancet Oncology, 10, 764-71, Lancet Oncology, 10, 8, pp. 764-71, Lancet Oncology, 10(8), 764-771. Lancet Publishing Group, Lancet Oncology, 10(8), 764-771. ELSEVIER SCIENCE INC, The lancet oncology
- Publication Year :
- 2009
-
Abstract
- Contains fulltext : 80017.pdf (Publisher’s version ) (Closed access) 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 la Sante et de la Recherche Medicale, and a PHRC grant COMETE 3 for the COMETE network.
- Subjects :
- Male
Pathology
endocrine system diseases
SDHB
FEATURES
DNA Mutational Analysis
SDHA
Adrenal Gland Neoplasms
HYPOXIA
MITOCHONDRIAL RESPIRATORY-CHAIN
Gene mutation
DISEASE
Paraganglioma
MALIGNANT PHEOCHROMOCYTOMAS
Medicine
Child
Cardiovascular diseases [NCEBP 14]
Syndrome
Middle Aged
Immunohistochemistry
Succinate Dehydrogenase
Mitochondrial respiratory chain
Oncology
Female
Carney Stratakis syndrome
Adult
medicine.medical_specialty
endocrine system
Adolescent
Blotting, Western
Pheochromocytoma
Article
Young Adult
Germline mutation
SDG 3 - Good Health and Well-being
ENZYMATIC-ACTIVITY
Humans
Germ-Line Mutation
Aged
COMPLEX-II
SUCCINATE
business.industry
Membrane Proteins
LINE MUTATIONS
medicine.disease
UPDATE
Human medicine
SDHD
business
Subjects
Details
- ISSN :
- 14745488 and 14702045
- Volume :
- 10
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- The Lancet. Oncology
- Accession number :
- edsair.doi.dedup.....ca5d4a20c2036bd3b4462f2b0a082f79