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

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.