title: PDGFRA immunostaining can help in the diagnosis of gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumors (GISTs) are characterized by the presence of activating mutations affecting the c-Kit or the PDGFRA gene. Although these mutations are mutually exclusive, their proteins are coexpressed in many GISTs with various modulations of immunostaining depending on which gene is mutated. CD117 expression is currently considered a sensitive (although not entirely specific) marker of KIT activation, but there is no consensus concerning the reliability of PDGFRA antibody. Our database contains 236 molecularly analyzed GISTs, and we here describe the 180 cases that underwent KIT/PDGFRA immunophenotyping. By correlating the immunophenotype with the molecular status of the genes expected to be involved, we observed the coexpression of KIT and PDGFRA in the majority of the mutated c-Kit and wild-type c-Kit/PDGFRA GISTs, whereas the -/+ immunophenotype (0% vs. 48.6%) and PDGFRA dotlike immunostaining (P<0.005) segregated with the PDGFRA-mutated GISTs. Taking either the dotlike decoration (26 cases) or -/+ immunophenotype (5 cases) as hallmarks of PDGFRA mutation, the presence of a PDGFRA mutation was predicted in 31 (83.8%) of the 37 PDGFRA mutated GISTs. Our findings suggest that, when critically applied, the routine use of CD117/PDGFRA immunophenotyping is a useful diagnostic tool (especially in CD117-negative cases) as it correctly predicts the presence of PDGFRA mutations in most cases.
authors: Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Francesca
authors: F
authors: Miselli
authors: Clara
authors: C
authors: Millefanti
authors: Elena
authors: E
authors: Conca
authors: Tiziana
authors: T
authors: Negri
authors: Cristina
authors: C
authors: Piacenza
authors: Marco A
authors: MA
authors: Pierotti
authors: Elena
authors: E
authors: Tamborini
authors: Silvana
authors: S
authors: Pilotti
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008637:Mesenchymoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha