Review ArticleStandardization of Positive Controls in Diagnostic Immunohistochemistry Recommendations From the International Ad Hoc Expert CommitteeTorlakovic, Emina E. MD, PhD*†; Nielsen, Søren HT, CT‡§; Francis, Glenn MBBS, FRCPA, MBA, FFSc (RCPA)∥¶#; Garratt, John RT†**; Gilks, Blake MD, FRCPC†††; Goldsmith, Jeffrey D. MD‡‡; Hornick, Jason L. MD, PhD*,§§; Hyjek, Elizabeth MD, PhD*; Ibrahim, Merdol PhD∥∥; Miller, Keith FIBMS∥∥; Petcu, Eugen MD, PhD∥; Swanson, Paul E. MD¶¶,##; Zhou, Xiaoge MD***,†††; Taylor, Clive R. MD, PhD‡‡‡; Vyberg, Mogens MD‡§Author Information *Department of Laboratory Hematology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON **Vancouver Costal Health ††Vancouver General Hospital/University of British Columbia, Vancouver, BC ##Department of Pathology, University of Calgary, Calgary, AB, Canada †Canadian Immunohistochemistry Quality Control (CIQC), Vancouver, BC, Canada ‡Institute of Pathology, Aalborg University Hospital, Denmark §Nordic Immunohistochemistry Quality Control (NordiQC), Aalborg, Denmark ∥Griffith University School of Medicine, Gold Coast Campus ¶Australian Institute for Bioengineering and Nano-Technology, University of Queensland, Qld, Australia #Convenor Immunohistochemistry, Anatomical Pathology Program, RCPA QAP Pty Ltd., Sydney, Australia ‡‡Beth Israel Deaconess Medical Center §§Brigham and Women’s Hospital, Harvard medical School, Boston, MA ∥∥UK National External Quality Assessment Scheme (UK NEQAS), University College London, London, UK ¶¶University of Washington, Seattle, WA ***Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China †††Chinese Committee for Pathology-Immunohistochemistry Quality Control (CCP-IHCQC) ‡‡‡Keck School of Medicine, University of Southern California, Los Angeles, CA E.E.T. and S.N. contributed equally. Supported in part by the following NIH/NCI Grants and contracts: 1R33 CA-10345; HHSN261201200044C. The authors declare no conflict of interest. Reprints: Emina E. Torlakovic, MD, PhD, Department of Laboratory Hematology, Toronto General Hospital, University Health Network, University of Toronto, Pathology, 11th Floor, R411, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4 (e-mail: [email protected]). Received October 31, 2014 Accepted November 1, 2014 Applied Immunohistochemistry & Molecular Morphology: January 2015 - Volume 23 - Issue 1 - p 1-18 doi: 10.1097/PAI.0000000000000163 Buy Metrics Abstract Diagnostic immunohistochemistry (dIHC) has been practiced for several decades, with an ongoing expansion of applications for diagnostic use, and more recently for detection of prognostic and predictive biomarkers. However, standardization of practice has yet to be achieved, despite significant advances in methodology. An Ad Hoc Expert Committee was formed to address the standardization of controls, which is a missing link in demonstrating and assuring standardization of the various components of dIHC. This committee has also developed a concept of immunohistochemistry critical assay performance controls that are intended to facilitate methodology transfer and harmonization in dIHC. Furthermore, the committee has clarified definitions of IHC assay sensitivity and specificity, with special emphasis on how these definitions apply to positive controls. Recommendations for “best laboratory practice” regarding positive controls for dIHC are specified. The first set of immunohistochemistry critical assay performance controls for several frequently used IHC stains or tests is also developed and presented. Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.