Interobserver variability of mitotic index and utility of PHH3 for risk stratification in gastrointestinal stromal tumors

Am J Clin Pathol. 2015 Mar;143(3):385-92. doi: 10.1309/AJCPAPH28VHZEKNQ.

Abstract

Objectives: Accurate grading of gastrointestinal stromal tumors (GISTs), based on mitotic index, can be problematic.

Methods: In this study, we compared interobserver variability in detecting mitosis on H&E with PHH3 immunohistochemistry (IHC). In addition, we examined the correlation between H&E mitosis and Ki-67 and the association of PHH3 and Ki-67 with overall survival. Four pathologists independently reviewed 50 GIST cases.

Results: Intraclass correlation coefficients showed good interobserver variability for mitotic counts on both H&E (0.918; 95% confidence interval [CI], 0.874-0.950) and PHH3 IHC (0.923; 95% CI, 0.882-0.953). Nineteen (38%) cases were graded higher and five (10%) cases were downgraded by at least one observer using PHH3 compared with H&E. Using receiver operating characteristic curve analysis, a PHH3 cutoff of seven or more mitoses was associated with worse overall survival (P = .028). Ki-67 showed poor correlation with H&E mitotic counts and overall survival (P = .077).

Conclusions: PHH3 may thus be a valuable adjunct for risk stratification in GISTs.

Keywords: Anti–phosphohistone H3; Gastrointestinal stromal tumors; Ki-67; Mitoses; Soft tissue.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Confidence Intervals
  • Female
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Neoplasms / pathology*
  • Gastrointestinal Stromal Tumors / metabolism
  • Gastrointestinal Stromal Tumors / mortality
  • Gastrointestinal Stromal Tumors / pathology*
  • Histones / chemistry
  • Histones / genetics*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / genetics*
  • Male
  • Middle Aged
  • Mitotic Index / statistics & numerical data*
  • Neoplasm Grading
  • Observer Variation
  • Phosphorylation
  • ROC Curve
  • Risk
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Histones
  • Ki-67 Antigen