title: Rhabdoid morphology in gastrointestinal stromal tumours (GISTs) is associated with PDGFRA mutations but does not imply aggressive behaviour.
abstract: OBJECTIVE
  Rhabdoid morphology resembling that of the aggressive paediatric rhabdoid tumours occurs in various malignancies usually lacking characteristic SMARCB1 (INI1) loss. Little is known about the clinicopathological and molecular characteristics of the rhabdoid phenotype in gastrointestinal stromal tumours (GISTs).
  
  
  RESULTS
  Six gastric rhabdoid GISTs were examined by immunohistochemistry, KIT and platelet-derived growth factor receptor-α gene (PDGFRA) mutation analysis, and comparative genomic hybridization (CGH). All tumours expressed KIT, PDGFRA, DOG-1, and SMARCB1 (two of six with a mosaic pattern). Five of six tumours harboured PDGFRA mutations (D842V in four; N659K in one), and one case was wild type for KIT/PDGFRA and succinate dehydrogenase (SDH) A-negative and SDHB-negative by immunohistochemistry. CGH revealed aberrations typical of GISTs (-1p, -14, and -22q in three, five, and three cases, respectively), with a mean of 1.7 aberrations in the epithelioid component and 2.7 in the rhabdoid component. None showed progression (mean follow-up of 25 months).
  
  
  CONCLUSIONS
  Rhabdoid gastric GISTs are associated with epithelioid morphology and PDGFRA mutations. They harbour CGH aberrations that are typical of ordinary GISTs in both tumour components. The presence of additional genetic alterations in the rhabdoid areas indicates evolution from the epithelioid components, and possible genetic and biological progression. On the basis of our series and previous reports, rhabdoid morphology in GISTs presumably does not imply aggressiveness.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Institute of Pathology, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Inga-Marie
authors.initials: IM
authors.lastname: Schaefer
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.forename: Alexander
authors.initials: A
authors.lastname: Beham
authors.forename: Claudia
authors.initials: C
authors.lastname: Otto
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
mesh_terms: D000328:Adult; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D000071796:SMARCB1 Protein; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: CGH; GIST; PDGFRA mutation; SDH; SMARCB1; gastric; rhabdoid