Abstract
The aims of this study were to investigate whether succinate dehydrogenase B (SDHB), insulin growth factor 1 receptor (IGF1R), HER2, epidermal growth factor receptor (EGFR) and/or BRAF V600E immunohistochemistry could screen for wild-type gastrointestinal stromal tumours (GISTs), and to determine what proportion of wild-type GISTs expressed these proteins and might therefore represent candidates for targeted therapies. Twenty-seven wild-type GISTs and 91 KIT-mutated or PDGFRA-mutated GISTs were immunostained for SDHB, IGF1R, HER2, and EGFR. A preliminary study of the BRAF VE1 antibody showed non-specific staining, and indicated it was neither a specific nor a sensitive marker of wild-type GISTs. SDHB loss showed 100% specificity but only 37% sensitivity as such a marker. EGFR and IGF1R were expressed by 63% and 33% of the wild-type GISTs but also by 56% and 32% of the KIT/PDGFRA mutant GISTs, respectively. Therefore, adding EGFR and/or IGF1R to SDHB as a panel only decreased the specificity of SDHB loss as a marker for wild-type status. All five antibodies failed, individually or collectively, to represent highly sensitive and highly specific markers for wild-type GIST. However, whereas HER2 has been excluded as a therapeutic biomarker, both EGFR and IGF1R are expressed by some wild-type GISTs and are therefore potential therapeutic targets.
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