Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: A comprehensive genotype-phenotype correlation study

Leona A. Doyle, Dylan Nelson, Michael Heinrich, Christopher Corless, Jason L. Hornick

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69 Citations (Scopus)

Abstract

Aims: Gastrointestinal stromal tumours (GISTs) typically harbour KIT or PDGFRA mutations; 15% of adult GISTs and >90% in children lack such mutations ('wild-type' GISTs). Paediatric and occasional adult GISTs show similar, distinctive features: multinodular architecture and epithelioid morphology, indolent behaviour with metastases, and imatinib resistance. Recent studies have suggested that these tumours can be identified by loss of succinate dehydrogenase subunit B (SDHB) expression. The aim of this study was to validate the predictive value of SDHB immunohistochemistry in a large genotyped cohort. Methods and results: SDHB expression was examined in GISTs with known genotypes: 179 with KIT mutations, 32 with PDGFRA mutations, and 53 wild type. Histological features were recorded without knowledge of genotype or SDHB status. SDHB was deficient in 22 (42%) wild-type GISTs. All other tumours showed intact SDHB expression. All SDHB-deficient GISTs with known primary sites arose in the stomach, and had multinodular architecture and epithelioid or mixed morphology. None of the wild-type GISTs with intact SDHB showed multinodular architecture, and only four (13%) had epithelioid morphology. Conclusions: SDHB-deficient GISTs are wild-type gastric tumours with distinctive histology. Immunohistochemistry for SDHB can be used to confirm the diagnosis of this tumour class. SDHB expression is retained in all GISTs with KIT and PDGFRA mutations.

Original languageEnglish (US)
Pages (from-to)801-809
Number of pages9
JournalHistopathology
Volume61
Issue number5
DOIs
StatePublished - Nov 2012

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Gastrointestinal Stromal Tumors
Succinate Dehydrogenase
Genetic Association Studies
Stomach
Mutation
Neoplasms
Immunohistochemistry
Genotype
Histology
Pediatrics
Neoplasm Metastasis

Keywords

  • Gastrointestinal stromal tumour
  • KIT
  • PDGFRA
  • Soft tissue sarcoma
  • Succinate dehydrogenase

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

@article{9ef6e3f90c6443b380bcee3aedd3762a,
title = "Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: A comprehensive genotype-phenotype correlation study",
abstract = "Aims: Gastrointestinal stromal tumours (GISTs) typically harbour KIT or PDGFRA mutations; 15{\%} of adult GISTs and >90{\%} in children lack such mutations ('wild-type' GISTs). Paediatric and occasional adult GISTs show similar, distinctive features: multinodular architecture and epithelioid morphology, indolent behaviour with metastases, and imatinib resistance. Recent studies have suggested that these tumours can be identified by loss of succinate dehydrogenase subunit B (SDHB) expression. The aim of this study was to validate the predictive value of SDHB immunohistochemistry in a large genotyped cohort. Methods and results: SDHB expression was examined in GISTs with known genotypes: 179 with KIT mutations, 32 with PDGFRA mutations, and 53 wild type. Histological features were recorded without knowledge of genotype or SDHB status. SDHB was deficient in 22 (42{\%}) wild-type GISTs. All other tumours showed intact SDHB expression. All SDHB-deficient GISTs with known primary sites arose in the stomach, and had multinodular architecture and epithelioid or mixed morphology. None of the wild-type GISTs with intact SDHB showed multinodular architecture, and only four (13{\%}) had epithelioid morphology. Conclusions: SDHB-deficient GISTs are wild-type gastric tumours with distinctive histology. Immunohistochemistry for SDHB can be used to confirm the diagnosis of this tumour class. SDHB expression is retained in all GISTs with KIT and PDGFRA mutations.",
keywords = "Gastrointestinal stromal tumour, KIT, PDGFRA, Soft tissue sarcoma, Succinate dehydrogenase",
author = "Doyle, {Leona A.} and Dylan Nelson and Michael Heinrich and Christopher Corless and Hornick, {Jason L.}",
year = "2012",
month = "11",
doi = "10.1111/j.1365-2559.2012.04300.x",
language = "English (US)",
volume = "61",
pages = "801--809",
journal = "Histopathology",
issn = "0309-0167",
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TY - JOUR

T1 - Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours

T2 - A comprehensive genotype-phenotype correlation study

AU - Doyle, Leona A.

AU - Nelson, Dylan

AU - Heinrich, Michael

AU - Corless, Christopher

AU - Hornick, Jason L.

PY - 2012/11

Y1 - 2012/11

N2 - Aims: Gastrointestinal stromal tumours (GISTs) typically harbour KIT or PDGFRA mutations; 15% of adult GISTs and >90% in children lack such mutations ('wild-type' GISTs). Paediatric and occasional adult GISTs show similar, distinctive features: multinodular architecture and epithelioid morphology, indolent behaviour with metastases, and imatinib resistance. Recent studies have suggested that these tumours can be identified by loss of succinate dehydrogenase subunit B (SDHB) expression. The aim of this study was to validate the predictive value of SDHB immunohistochemistry in a large genotyped cohort. Methods and results: SDHB expression was examined in GISTs with known genotypes: 179 with KIT mutations, 32 with PDGFRA mutations, and 53 wild type. Histological features were recorded without knowledge of genotype or SDHB status. SDHB was deficient in 22 (42%) wild-type GISTs. All other tumours showed intact SDHB expression. All SDHB-deficient GISTs with known primary sites arose in the stomach, and had multinodular architecture and epithelioid or mixed morphology. None of the wild-type GISTs with intact SDHB showed multinodular architecture, and only four (13%) had epithelioid morphology. Conclusions: SDHB-deficient GISTs are wild-type gastric tumours with distinctive histology. Immunohistochemistry for SDHB can be used to confirm the diagnosis of this tumour class. SDHB expression is retained in all GISTs with KIT and PDGFRA mutations.

AB - Aims: Gastrointestinal stromal tumours (GISTs) typically harbour KIT or PDGFRA mutations; 15% of adult GISTs and >90% in children lack such mutations ('wild-type' GISTs). Paediatric and occasional adult GISTs show similar, distinctive features: multinodular architecture and epithelioid morphology, indolent behaviour with metastases, and imatinib resistance. Recent studies have suggested that these tumours can be identified by loss of succinate dehydrogenase subunit B (SDHB) expression. The aim of this study was to validate the predictive value of SDHB immunohistochemistry in a large genotyped cohort. Methods and results: SDHB expression was examined in GISTs with known genotypes: 179 with KIT mutations, 32 with PDGFRA mutations, and 53 wild type. Histological features were recorded without knowledge of genotype or SDHB status. SDHB was deficient in 22 (42%) wild-type GISTs. All other tumours showed intact SDHB expression. All SDHB-deficient GISTs with known primary sites arose in the stomach, and had multinodular architecture and epithelioid or mixed morphology. None of the wild-type GISTs with intact SDHB showed multinodular architecture, and only four (13%) had epithelioid morphology. Conclusions: SDHB-deficient GISTs are wild-type gastric tumours with distinctive histology. Immunohistochemistry for SDHB can be used to confirm the diagnosis of this tumour class. SDHB expression is retained in all GISTs with KIT and PDGFRA mutations.

KW - Gastrointestinal stromal tumour

KW - KIT

KW - PDGFRA

KW - Soft tissue sarcoma

KW - Succinate dehydrogenase

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