Precision medicine implies precision pathology, which in turn invokes the use of a new range of advanced diagnostic tests in pathology laboratories that are variously termed “companion diagnostics,” “predictive diagnostics,” “precision diagnostics,” “theranostics,” and “advanced personalized diagnostics.” Companion diagnostics typically aim to detect “predictive biomarkers,” for which the level of expression detected in a tumor may be of value in classifying patients into “responders” and “non-responders” with respect to the specified targeted therapy.
Over the past 4 decades immunohistochemistry (IHC) has primarily been employed to provide a broad range of “special stains” that are mostly used for classification of tumors in FFPE tissues. If success is to be measured in terms of the number of different “IHC stains” that are in daily use, then the IHC method must be judged a resounding success. However, the success of the method conceals major deficiencies in practice.
In 1998, approval of the Her2 test as a companion diagnostic for Herceptin therapy marked the beginning of this era of precision medicine. However, the enhanced levels of performance that are required represent a real challenge for the IHC method, and the problems of poor test reproducibility have been revisited time and time again. By analogy with ELISA in the clinical laboratory, automation of both the technical performance and the reading of IHC results for companion diagnostics is inevitable.
The expanding use of automated staining platforms, coupled with integrated QA and QC systems, effectively guarantees that reagents and protocols will be subject to increasingly rigorous validation, using closed assay systems that cannot be “tweaked” in order to produce more intense staining as a means of to compensating for a ‘weak result’ due to deficient FFPE tissue processing. Also most companion diagnostics demand some degree of quantification, extending beyond the semi-quantitative manual scoring methods used in the first HER2 tests. Digital whole slide image analysis for consistent and accurate reading of results is likely to provide the intelligent microscope of the near future.
It is proposed that IHC can be upgraded from its use as a qualitative special stain to an accurate and reliable quantitative ‘tissue-based immunologic assay’ (in situ proteomics), analogous to the use of the ELISA method in the clinical laboratory. These rapidly advancing changes represent an opportunity that it will be dangerous to ignore.
Professor Clive Roy Taylor holds M.A. and M.D. degrees from the University of Cambridge, and M.A. and D. Phil degrees from the University of Oxford. Dr. Taylor was appointed Lecturer in the Department of Pathology at the University of Oxford, in 1970. A “Traveling Fellowship” in Cancer Research took Dr. Taylor to the University of Southern California in 1975, where he subsequently was appointed to the Chair of the Department of Pathology in 1984, a position that he held for 25 years. In 1998 Professor Taylor accepted the post of Senior Associate Dean for Educational Affairs at the Keck School of Medicine, a role that he filled until 2009. Professor Taylor is a Fellow of the Royal College of Pathologists (U.K.), a Diplomate of the American Board of Pathology, a Member of the Royal College of Physicians (Ireland), and a Member of the Royal Society of Medicine. Professor Taylor Chaired an FDA Advisory Panel for Diagnostic Devices and Radiology until 2007. His primary research relates to advanced methods of diagnosis and treatment of cancer, by immunologic and molecular methods. He has published more than 400 scientific papers and 12 books and has maintained external research funding from the National Institutes of Health Innovative Molecular Analysis Technologies program. Dr. Taylor holds several patents. He is Editor-in-Chief of Applied Immunohistochemistry and Molecular Morphology, is a Trustee and Past President of the US. Biological Stain Commission, and has served as a Board member and / or consultant to a number of private and public corporations. Dr. Taylor is married with four children, all of whom are physicians.
Gu J. Taylor CR. Practicing pathology in the era of big data and personalized medicine. Appl Immunohistochem Mol Morph. 22; 1-9; 2014.
Taylor CR.Predictive Biomarkers and Companion Diagnostics.The Future of Immunohistochemistry – ‘in situ proteomics’, or just a ‘stain’? Applied Immunohistochem Mol Morph. 2014; 22:555-561.
Taylor CR. Quantitative In Situ Proteomics; a proposed pathway for quantification of immunohistochemistry at the light-microscopic level.” Cell Tissue Res. 2015; 360:109-120.
Cheung. CC et al Taylor CR. Evolution of Quality Assurance of Clinical Immunohistochemistry in the Era of Precision Medicine – Part 1: Fit-for-purpose Approach to Classification of Clinical Immunohistochemistry Tests. Applied Immunohistochem Mol Morph.2017. Part 1 of 4 – In Press.