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

• Published in: American journal of clinical pathology Vol. 143; no. 3; pp. 385 - 392
• Main Authors: Alkhasawneh, Ahmad, Reith, John D., Toro, Tania Zuluaga, Ayed, Ayed O., Lu, Xiaomin, George, Thomas J., Duckworth, Lizette Vila
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford University Press 01.03.2015
• Subjects: 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; Risk; ROC Curve; Survival Analysis; Ki-67; Mitoses; Gastrointestinal stromal tumors; Soft tissue; Anti–phosphohistone H3; Mitoses; Soft tissue
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1309/AJCPAPH28VHZEKNQ

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.