title: Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes.
abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Approximately 85% of GISTs harbor activating mutations in the KIT or platelet-derived growth factor receptor alpha (PDGFRA) gene and approximately 95% of GISTs are positive for KIT (CD117) by immunohistochemistry. Nevertheless, approximately 5% of GISTs lack KIT expression. Inhibition of KIT and PDGFRA by tyrosine kinase inhibitors has revolutionized the treatment of GISTs and demands accurate tumor classification. DOG1.1 is a recently described mouse monoclonal antibody reported to have superior sensitivity and specificity compared with KIT (CD117) and CD34. We evaluated this new antibody on a group of 81 GISTs obtained from 74 patients with special regard to KIT-negative GISTs (n=28), pediatric GISTs (n=11), and GISTs associated with neurofibromatosis type I (NF1) (n=16). Conventional GISTs (n=26) were also included. All conventional KIT-positive GISTs, all NF1-associated GISTs, and 9/11 pediatric GISTs expressed DOG1.1. DOG1.1 was expressed in 10/28 (36%) of KIT-negative tumors. The staining pattern was cytoplasmic and/or membranous. This study demonstrates that DOG1.1 is a sensitive immunohistochemical marker for GIST, comparable with KIT, with the additional benefit of detecting 36% of KIT-negative GISTs. DOG1.1 is also a sensitive marker for unusual GIST subgroups lacking KIT or PDGFRA mutations. In tumors that are negative for both KIT and DOG1.1, mutational screening may be required to confirm the diagnosis of GIST.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D000368:Aged; D000075369:Anoctamin-1; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34 / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018118:Chloride Channels; D004252:DNA Mutational Analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha