Exon 11 mutations, Ki67, and p16(INK4A) as predictors of prognosis in patients with GIST

Pathol Res Pract. 2011 Nov 15;207(11):701-6. doi: 10.1016/j.prp.2011.09.008. Epub 2011 Oct 24.

Abstract

Prognostic biomarkers for GIST are under investigation. The aim of this study was to assess whether exon 11 mutations, Ki67, and p16(INK4A) are predictors of prognosis in GIST. Consecutive GIST cases (n=84) had their specimens evaluated for exon 11 mutations and expression of Ki67 and p16(INK4A). Surgical cases were categorized according to NIH and Miettinen's classification, and survival was analyzed from hospital database. GISTs were predominately gastric (45%) and with spindle cell morphology (74%). The risk category was very low or low in 28%, intermediate in 23%, and high in 49%. Exon 11 mutation was identified in 29 (48%) out of 60 cases studied. There were 12 point mutations, 10 deletions, 4 duplications, and 3 double mutations. A third of GISTs had either high Ki67 index (>3%) or negativity for p16(INK4A). In multivariate analysis, independent predictors of mortality were Ki67>3% (HR=7.3; P=0.036) and high mitotic index (HR=10.4; P=0.043). There was no association between exon 11 mutations and survival. This study suggests that Ki67>3% is an independent predictor of poor prognosis in patients with GIST. Exon 11 mutations and negativity for p16(INK4A) need further studies to address the prognostic value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA, Neoplasm / genetics
  • Exons / genetics
  • Female
  • Follow-Up Studies
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / mortality*
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / metabolism
  • Gastrointestinal Stromal Tumors / mortality*
  • Genetic Testing
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / genetics*
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Mitotic Index
  • Multivariate Analysis
  • Mutation
  • Prognosis
  • Sensitivity and Specificity
  • Sequence Analysis, DNA
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • Ki-67 Antigen