Proteomics: Adding a dimension to cancer tissue pathology

Abstract

The detection of specific proteins in cancer tissue by immunohistochemistry has long been a mainstay of diagnostic pathology. More recently, various forms of ‘molecular analysis’ have evolved for diagnostic use, principally consequent to rapid progress in high-throughput analysis of DNA and RNA. Proteins are the chief structural and effector molecules in tissues, and interaction with proteins is the mechanism of action of many drugs. It is likely that further progress will come from a detailed understanding of the tissue proteome, however to date methods for reproducible proteomic analysis have been lacking. Mass spectrometry (MS) is a method that can be used to detect specific protein fragments (peptides) in tissue on the basis of their physico-chemical properties. By alignment to reference databases, a semi-quantitative assessment of tissue protein content can be derived that is amenable to big-data analytic approaches. A challenge is that MS analysis is tissue disruptive. It is critical that the tissue content of samples is documented so that proteomic data can be interpreted in the context of histopathology. Whole slide imaging (digital pathology) has a role as an important adjunct to tissue proteomics. Co-development of these technologies can facilitate both discovery proteomics and implementation into clinical practice.