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Updated: Apr 17, 2026

Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Interobserver variability of mitotic index and utility of PHH3 for risk stratification in gastrointestinal stromal
Ahmad Alkhasawneh1, John D Reith1, Tania Zuluaga Toro1
1From the Department of Pathology, Immunology and Laboratory Medicine.
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.
