A ‘companion diagnostic’ is a test for a predictive biomarker, that classifies patients (tumors) into responders and non-responders, for a specified therapeutic agent. Companion diagnostics are designated as Class III medical devices by the FDA, because the test result equates directly to administration of a drug.
Testing for HER2 expression was approved by the FDA in 1998, and served as the prototype for using immunohistochemistry (IHC) as the basis for a companion diagnostic. However, over four decades IHC has primarily been employed in a broad range of ‘special stains’, for identification and classification cells and tumors in FFPE (formalin fixed paraffin embedded) tissues. During the long use of IHC as a ‘special stain’ we have acquired some very bad habits, changing protocols, concentrations, incubation times, retrieval methods, or reagents, to achieve the perception of a ‘good’ stain, that ‘pleases the eye’ of the user pathologist. While this approach may be acceptable for IHC stains, it is a recipe for disaster when transferred to companion diagnostics, where quantification and absolute reproducibility are required. In the context of companion diagnostics the IHC method should be regarded as an assay, not simply a stain. Elevating IHC to a true immunoassay will necessitate a much more rigorous approach to performance, reproducibility and control. The ultimate goal is to supplement morphologic judgment with precise measurement of proteins in tissues and in individual cells, ‘in situ proteomics’ as it were.