title: An immunohistochemical study of potential diagnostic and therapeutic biomarkers of wild-type gastrointestinal stromal tumours.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Histopathology, Bristol Royal Infirmary, Bristol, UK.
authors: Newton A C S
authors: NA
authors: Wong
authors: Department of Histopathology, Bristol Royal Infirmary, Bristol, UK.
authors: Jenny
authors: J
authors: Wingate
authors: Department of Histopathology, Bristol Royal Infirmary, Bristol, UK.
authors: Elise
authors: E
authors: Gradhand
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin; D013385:Succinate Dehydrogenase; C000597236:IGF1R protein, human; C108095:SDHB protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human
keywords: BRAF; EGFR; ERBB2; IGF type 1; SDHB; gastrointestinal stromal tumours; genotype; immunohistochemistry; receptor