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. PATIENTS AND 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.
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. PATIENTS AND 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: J F Emile; S Brahimi; J M Coindre; P P Bringuier; G Monges; P Samb; L Doucet; I Hostein; B Landi; M P Buisine; A Neuville; O Bouché; P Cervera; J L Pretet; J Tisserand; A Gauthier; A Le Cesne; J C Sabourin; J Y Scoazec; S Bonvalot; C L Corless; M C Heinrich; J Y Blay; P Aegerter Journal: Med Oncol Date: 2011-09-28 Impact factor: 3.064
Authors: Christopher L Corless; Karla V Ballman; Cristina R Antonescu; Violetta Kolesnikova; Robert G Maki; Peter W T Pisters; Martin E Blackstein; Charles D Blanke; George D Demetri; Michael C Heinrich; Margaret von Mehren; Shreyaskumar Patel; Martin D McCarter; Kouros Owzar; Ronald P DeMatteo Journal: J Clin Oncol Date: 2014-03-17 Impact factor: 44.544
Authors: Brian K Bednarski; Dejka M Araujo; Min Yi; Keila E Torres; Alexander Lazar; Jonathan C Trent; Janice N Cormier; Peter W T Pisters; Dina Chelouche Lev; Raphael E Pollock; Barry W Feig; Kelly K Hunt Journal: Ann Surg Oncol Date: 2014-03-18 Impact factor: 5.344
Authors: J Martin-Broto; V Martinez-Marín; C Serrano; N Hindi; J A López-Guerrero; R Ramos-Asensio; A Vallejo-Benítez; D Marcilla-Plaza; R González-Cámpora Journal: Clin Transl Oncol Date: 2016-12-09 Impact factor: 3.405