Comprehensive Immunohistochemistry: Digital, Analytical and Integrated.

Immunohistochemistry (IHC) is widely used in contemporary pathology as a diagnostic and, increasingly, as a prognostic and predictive tool. The main value of the method today comes from a sensitive and specific detection of a protein of interest in the context of tissue architecture and cell populations. One of the major limitations of conventional IHC is related to the fact that the results are usually obtained by visual qualitative or semiquantitative evaluation. While this is sufficient for diagnostic purposes, measurement of prognostic and predictive biomarkers requires better accuracy and reproducibility. Also, objective evaluation of the spatial heterogeneity of biomarker expression as well as the development of combined/integrated biomarkers are in great demand. On the other end of the scale, the rapid development of tissue proteomics accounting for 2D spatial aspects has led to a disruptive concept of next-generation IHC, promising high multiplexing and broad dynamic range quantitative/spatial data on tissue protein expression. This 'evolutionary gap' between conventional and next-generation IHC can be filled by comprehensive IHC based on digital technologies (empowered by quantification and spatial and multiparametric analytics) and integrated into the pathology workflow and information systems. In this paper, we share our perspectives on a comprehensive IHC road map as a multistep development process.