title: Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKCθ expression. Is there any advantage in using several markers?
abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKCθ was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to determine the sensitivity and diagnostic value of these markers. KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were amplified by PCR and sequenced. A total of 94/99 (94%) GISTs stained positive for CD117, 81/99 (82%) for PKCθ and 90/99 (91%) for DOG-1. A significant correlation was noted between CD117 and DOG-1 expression (p=0.0001). All three markers were expressed in 74% (73/99) of GISTs. Of the five CD117-negative cases, two were PKCθ-negative/DOG1-negative and had mutations in KIT exon 11. Two were PKCθ-positive/DOG1-positive and had mutations in PDGFRA (one each in exons 12 and 18), and one was DOG1-negative/PKCθ-positive, with a PDGFRA exon 18 mutation. The most sensitive marker was CD117, followed by DOG-1 and PKCθ. Although PKCθ was less sensitive, and its staining is more challenging and difficult to interpret, the use of this marker is highly recommended, particularly in CD117-negative/DOG-1-negative GISTs.
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario Virgen Macarena, Seville, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ríos-Moreno
authors.forename: S
authors.initials: S
authors.lastname: Jaramillo
authors.forename: S
authors.initials: S
authors.lastname: Pereira Gallardo
authors.forename: A
authors.initials: A
authors.lastname: Vallejo
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: A
authors.initials: A
authors.lastname: García-Escudero
authors.forename: J
authors.initials: J
authors.lastname: Amérigo
authors.forename: R
authors.initials: R
authors.lastname: González-Cámpora
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016009:Chi-Square Distribution; D018118:Chloride Channels / Q000032:analysis*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis*; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D011493:Protein Kinase C / Q000032:analysis*; D000074121:Protein Kinase C-theta; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis* / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012680:Sensitivity and Specificity; D013030:Spain; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D007527:Isoenzymes; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta