Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study

Ann Oncol. 2010 Jul;21(7):1552-1557. doi: 10.1093/annonc/mdq047. Epub 2010 Mar 15.

Abstract

Background: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up.

Patients and methods: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT.

Results: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months.

Conclusion: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Codon / genetics*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Proto-Oncogene Proteins c-kit / genetics*
  • Sequence Deletion / genetics*
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Codon
  • Proto-Oncogene Proteins c-kit