Not all patients respond well to treatment and drugs have failed in the clinic due to “all patient” designs. As a result drugs that could help subpopulations of patients may never make it to market. Identifying patients and stratifying them according to their likelihood as responders can guide clinical trial design, leading to more success in the clinic and ultimately increasing the range and personalisation of treatments available.
Immunohistochemistry (IHC) could be used to group patients according to the expression levels of a specific biomarker. With more emphasis on standardisation, reliability, validation and quantification, IHC assays can play this role in patient stratification.
IHC assays are not easily validated - hindered not least by the lack of standardisation in tissue collection, handling and fixation[1,2,3]. Availability of specific and reliable antibodies is the crux of successful assay development and much time can be spent identifying the best reagent. Furthermore, Moulis highlights that IHC assays are generally optimised to the strongest level of expression when they actually need to be optimised around the dynamic range of the biomarker (i.e. the range of possible levels of expression) in order for them to be useful and fit-for-purpose. In personalised medicine, the dynamic range of expression needs to be known to determine cut-off points and subsequently stratify patients. Therefore, more emphasis and evaluation of assay performance on low, medium and high expressing controls in the form of cell lines and tissues would be beneficial if not necessary.
Traditionally IHC is a qualitative rather than quantitative assay but has always been considered valuable due to its tissue-rich context and ability to demonstrate expression in situ. Accurate and reproducible quantification of IHC could fill the gap and leave IHC an unrivalled assay in comparison to the inherently quantitative but liquid-based assays like Western Blotting and ELISAs. Conventionally, semi-quantitative scoring is generally performed visually by a pathologist and while good correlation has been demonstrated, quantification achieved through image analysis can produce much more precise measurements (See Figs 1 and 2). With successful validation and quantification, IHC assays can play a vital role in drug development as a method of patient stratification.
 Definiens Webinar: Clinical Trial Patient Stratification with Quantitative IHC Assays Patient. Sharon Moulis 13 May 2015
 Definiens: Redefining IHC Assays for Powerful, Quantification, Patient Stratification and Companion Diagnostics
 Biomarkers for Patient Stratification. Brussels 10 – 11 Jun 2010
 Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring. Rizzardi AE, Johnson AT, Vogel RI, Pambuccian SE, Henriksen J, Skubitz AP, Metzger GJ, Schmechel SC. Diagn Pathol. 2012 Jun 20;7:42. doi: 10.1186/1746-1596-7-42.