title: Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience.
abstract: BACKGROUND
  Majority of gastrointestinal stromal tumours (GISTs) are characterised by KIT-immunopositivity and the presence of KIT/platelet-derived growth factor receptor alpha (PDGFRA) activating mutations.
  
  
  METHODS
  Spectrum and frequency of KIT and PDGFRA mutations were investigated in 427 GISTs. Univariate and multivariate analysis of relapse-free survival (RFS) was conducted in relation to tumours' clinicopathologic features and genotype.
  
  
  RESULTS
  Mutations were found in 351 (82.2%) cases, including 296 (69.3%) KIT and 55 (12.9%) PDGFRA isoforms. Univariate analysis revealed higher 5-year RFS rate in women (37.9%; P = 0.028) and in patients with gastric tumours (46.3%; P < 0.001). In addition a better 5-year RFS correlated with smaller tumour size ≤ 5 cm (62.7%; P < 0.001), tumours with mitotic index ≤ 5/50 high-power fields (60%; P < 0.001), and characterised by (very) low/moderate risk (70.2%; P = 0.006). Patients with GISTs bearing deletions encompassing KIT codons 557/558 had worse 5-year RFS rate (23.8%) than those with any other KIT exon 11 mutations (41.8%; P < 0.001) or deletions not involving codons 557/558 (33.3%; P = 0.007). Better 5-year RFS characterised patients with KIT exon 11 point mutations (50.7%) or duplications (40%). By multivariate analysis, tumours with PDGFRA mutations and KIT exon 11 point mutations/other than 557/558 deletions had lower risk of progression than with KIT exon 11 557/558 deletions (both Ps = 0.001).
  
  
  CONCLUSIONS
  KIT/PDGFRA mutational status has prognostic significance for patients' outcome and may help in management of patients with GISTs.
authors.affiliation: Department of Biology and Genetics, Medical University of Gdansk, Gdansk, Poland. agnieszka.wozniak@med.kuleuven.be
authors.forename: A
authors.initials: A
authors.lastname: Wozniak
authors.forename: P
authors.initials: P
authors.lastname: Rutkowski
authors.forename: A
authors.initials: A
authors.lastname: Piskorz
authors.forename: M
authors.initials: M
authors.lastname: Ciwoniuk
authors.forename: C
authors.initials: C
authors.lastname: Osuch
authors.forename: E
authors.initials: E
authors.lastname: Bylina
authors.forename: J
authors.initials: J
authors.lastname: Sygut
authors.forename: M
authors.initials: M
authors.lastname: Chosia
authors.forename: J
authors.initials: J
authors.lastname: Rys
authors.forename: K
authors.initials: K
authors.lastname: Urbanczyk
authors.forename: W
authors.initials: W
authors.lastname: Kruszewski
authors.forename: P
authors.initials: P
authors.lastname: Sowa
authors.forename: J
authors.initials: J
authors.lastname: Siedlecki
authors.forename: M
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: J
authors.initials: J
authors.lastname: Limon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha