Interobserver Variability of Mitotic Index and Utility of PHH3 for Risk Stratification in Gastrointestinal Stromal Tumors

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.