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

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.