An immunohistochemical study of potential diagnostic and therapeutic biomarkers of wild‐type gastrointestinal stromal tumours

Aims The aims of this study were to investigate whether succinate dehydrogenase B ( SDHB ), insulin growth factor 1 receptor ( IGF 1R), HER 2, epidermal growth factor receptor ( EGFR ) and/or BRAF V600E immunohistochemistry could screen for wild‐type gastrointestinal stromal tumours ( GIST s), and to determine what proportion of wild‐type GIST s expressed these proteins and might therefore represent candidates for targeted therapies. Methods and results Twenty‐seven wild‐type GIST s and 91 KIT ‐mutated or PDGFRA ‐mutated GIST s were immunostained for SDHB , IGF 1R, HER 2, and EGFR . A preliminary study of the BRAF VE 1 antibody showed non‐specific staining, and indicated it was neither a specific nor a sensitive marker of wild‐type GIST s. SDHB loss showed 100% specificity but only 37% sensitivity as such a marker. EGFR and IGF 1R were expressed by 63% and 33% of the wild‐type GIST s but also by 56% and 32% of the KIT/PDGFRA mutant GIST s, respectively. Therefore, adding EGFR and/or IGF 1R to SDHB as a panel only decreased the specificity of SDHB loss as a marker for wild‐type status. Conclusions All five antibodies failed, individually or collectively, to represent highly sensitive and highly specific markers for wild‐type GIST . However, whereas HER 2 has been excluded as a therapeutic biomarker, both EGFR and IGF 1R are expressed by some wild‐type GIST s and are therefore potential therapeutic targets.