title: Interobserver variability of mitotic index and utility of PHH3 for risk stratification in gastrointestinal stromal tumors.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Pathology, Immunology and Laboratory Medicine.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alkhasawneh
authors.affiliation: From the Department of Pathology, Immunology and Laboratory Medicine.
authors.forename: John D
authors.initials: JD
authors.lastname: Reith
authors.affiliation: From the Department of Pathology, Immunology and Laboratory Medicine.
authors.forename: Tania Zuluaga
authors.initials: TZ
authors.lastname: Toro
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, and.
authors.forename: Ayed O
authors.initials: AO
authors.lastname: Ayed
authors.affiliation: Department of Biostatistics, University of Florida College of Medicine, Gainesville.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, and.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: George
authors.affiliation: From the Department of Pathology, Immunology and Laboratory Medicine, lvila@pathology.ufl.edu.
authors.forename: Lizette Vila
authors.initials: LV
authors.lastname: Duckworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016001:Confidence Intervals; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006657:Histones / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index / Q000706:statistics & numerical data*; D060787:Neoplasm Grading; D015588:Observer Variation; D010766:Phosphorylation; D012372:ROC Curve; D012306:Risk; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D019394:Ki-67 Antigen
keywords: Anti–phosphohistone H3; Gastrointestinal stromal tumors; Ki-67; Mitoses; Soft tissue