title: Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS).
abstract: OBJECTIVE
  To explore the prognostic value of mutations in c-KIT and PDGFR-alpha genes with respect to relapse-free survival (RFS) in patients with gastrointestinal stromal tumors (GIST). We have investigated the prognostic relevance of the type and position of the mutations, in addition to other clinicopathologic factors, in a large series of patients with GIST.
  
  
  METHODS
  For this study, 162 patients were selected according to the following criteria: completely resected tumors with negative margins attended between 1994 and 2001; no metastasis at diagnosis; tumor larger than 2 cm, c-KIT-positive immunostaining; and no other primary tumors.
  
  
  RESULTS
  The median follow-up was 42 months for patients free of recurrence. Mutations were detected in 96 tumors (60%): 82 cases involving c-KIT and 14 cases involving PDFGR-alpha. Univariate analysis demonstrated the following as poor prognostic factors for RFS: tumors larger than 10 cm (P < .0001); mitotic count higher than 10 mitoses per 50 high-power fields (P < .0001); high risk index (P < .0001); intestinal GIST location (P = .0041); high cellularity (P < .0001); tumor necrosis (P < .0001); deletions affecting exon 11 (P = .0007); and deletions affecting codons 557 to 558 (P < .0001). After the multivariate analysis, only the high risk index (relative risk [RR], 12.36), high cellularity (RR, 3.97), and deletions affecting codons 557 to 558 of c-KIT (RR, 2.57) corresponded to independent prognostic factors for RFS in GIST patients.
  
  
  CONCLUSIONS
  Deletions affecting codons 557 to 558 are relevant for the prognosis of RFS in GIST patients. This critical genetic alteration should be considered to be a new prognostic stratification variable for randomized trials exploring imatinib mesylate in the adjuvant setting in GIST patients.
authors.affiliation: Department of Oncology, Hospital Universitario de Son Dureta, C/Andrea Doria 55, 07014 Palma de Mallorca (Baleares), Spain. jmartin@hsd.es
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Andrés
authors.initials: A
authors.lastname: Poveda
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramos
authors.forename: José A
authors.initials: JA
authors.lastname: López-Guerrero
authors.forename: Javier
authors.initials: J
authors.lastname: García del Muro
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.forename: Silvia
authors.initials: S
authors.lastname: Calabuig
authors.forename: Antonio
authors.initials: A
authors.lastname: Gutierrez
authors.forename: José L
authors.initials: JL
authors.lastname: González de Sande
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez
authors.forename: Ana
authors.initials: A
authors.lastname: De Juan
authors.forename: Nuria
authors.initials: N
authors.lastname: Laínez
authors.forename: Ferrán
authors.initials: F
authors.lastname: Losa
authors.forename: Valentín
authors.initials: V
authors.lastname: Alija
authors.forename: Pilar
authors.initials: P
authors.lastname: Escudero
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado
authors.forename: Paula
authors.initials: P
authors.lastname: García
authors.forename: Pilar
authors.initials: P
authors.lastname: García
authors.forename: Remei
authors.initials: R
authors.lastname: Blanco
authors.forename: José M
authors.initials: JM
authors.lastname: Buesa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D003062:Codon; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha