title: Loss of DOG-1 expression associated with shift from spindled to epithelioid morphology in gastric gastrointestinal stromal tumors with KIT and platelet-derived growth factor receptor α mutations.
abstract: Most gastric gastrointestinal stromal tumors (GISTs) display spindle cell morphology and coexpress CD117 (KIT), DOG-1, and CD34. Secondary loss of DOG-1 has not been reported. We present two gastric GISTs which showed loss of DOG-1 in the epithelioid component but retained its expression in the minor spindle cell component. Patients were a 67-year-old man and an 80-year-old woman with 4.8-cm and 3.5-cm gastric GISTs harboring mutations in KIT exon 11 (c.1729_1758dup30; p.P577_R586dup) and platelet-derived growth factor receptor α (PDGFRA) exon 18 (c.2527_2538del12; p.I843_D846del), respectively. Both were predominantly epithelioid with a minor microscopic spindle cell component (3-12 mm). The spindle cell component was CD117(+)CD34(+)DOG-1(+) in both cases. The epithelioid component in case 1 was CD117(+)CD34(+)DOG-1(-). In case 2, the epithelioid component strongly expressed PDGFRA (dot-like) but lost CD117, CD34, and DOG-1. These cases confirm the immunophenotypic heterogeneity as secondary events in GIST. Loss of DOG-1 in KIT-negative PDGFRA mutants should not preclude diagnosis.
authors.affiliation: Institute of Pathology, University Hospital, Erlangen, Germany. abbas.agaimy@uk-erlangen.de
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Lai Mun
authors.initials: LM
authors.lastname: Wang
authors.forename: Matthias
authors.initials: M
authors.lastname: Eck
authors.forename: Florian
authors.initials: F
authors.lastname: Haller
authors.forename: Runjan
authors.initials: R
authors.lastname: Chetty
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000075369:Anoctamin-1; D001483:Base Sequence; D018118:Chloride Channels / Q000096:biosynthesis*; D004252:DNA Mutational Analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha