Research ArticlesImmunohistochemistry Critical Assay Performance Controls (ICAPC) Reduce Interobserver Variability in the Interpretation of BRAFV600E ImmunohistochemistryGale, Nadia S. MLT (CSMLS)*; Kalloger, Steve E. MSc†,‡; Cai, Ellen MD†; Abozina, Alisa MD†; Derakhshan, Fatameh MD†; Hickey, Tyler MD†; Liu, Ariel MD†; Ongaro, Deidre MD†; Wolber, Robert MD*,†; Schaeffer, David F. MD, PhD*,†Author Information *Department of Pathology & Laboratory Medicine, Vancouver Coastal Health †Department of Pathology & Laboratory Medicine ‡School of Population & Public Health, University of British Columbia, Vancouver, BC, Canada N.S.G., S.E.K., and E.C.: contributed equally. D.F.S. reports consultant fees from Provincial Health Services Authority (BC Colon Cancer Screening Program) and scientific advisory board fees from Amgen as well as consultant fees from Robarts Clinical Trials Inc. The remaining authors declare no conflict of interest. Reprints: Steve E. Kalloger, MSc, P.O. Box 48352, Vancouver, BC, Canada V7X 1A1 (e-mail: firstname.lastname@example.org). Applied Immunohistochemistry & Molecular Morphology: July 2020 - Volume 28 - Issue 6 - p 422-427 doi: 10.1097/PAI.0000000000000784 Buy Metrics Abstract The utility of prognostic and predictive immunohistochemistry biomarkers in the context of cancer is plagued by inconsistent interpretation of results which can lead to poor rates of adoption or inappropriate use of novel therapeutic strategies. To monitor immunohistochemistry assay performance, a new on-slide control motif, Immunohistochemistry Critical Assay Performance Controls (ICAPC) was developed. We hypothesized that the use of these controls by the diagnosing pathologist to interpret BRAFV600E would result in reduced interobserver and intraobserver interpretation errors. A cross-sectional, sequentially obtained sample of surgical pathology cases stained for BRAFV600E was assembled from a single hospital in Vancouver, British Columbia. Half of the cases had normal on-slide controls and the remainder with ICAPC. Results from 6 independent and blinded readers were compared with each other and to the gold-standard pathologic diagnosis with the goal of demonstrating superior interrater agreement with ICAPC relative to standard on-slide controls. Cohen’s κ was used to compute pair-wise reader agreements, whereas Fleiss’ κ was used to compare to the gold standard. The implementation of ICAPC resulted in statistically significant improvements in the interobserver agreement of BRAF mutation status ascertained by BRAFV600E immunohistochemistry. Half of the readers demonstrated significant improvements in agreement with the gold-standard diagnosis with the addition of ICAPC. Across all readers, the mean increase in κ was 0.14 with a 95% confidence interval of 0.01-0.28 (P=0.04). This study demonstrates that the addition of ICAPC serves to significantly reduce interobserver variability in the assessment of BRAFV600E immunohistochemistry. As such, we recommend that this approach should be used as part of a comprehensive quality management strategy in the setting of histopathology. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.