Unlocking the molecular archive: the emerging use of formalin-fixed paraffin-embedded tissue for biomarker research...

Rapid developments have been made in identifying predictive and prognostic markers in urological cancers. Most biomarker profiling has been primarily conducted in fresh-frozen tissue taken at the time of diagnosis or surgery. The disadvantage of this process is that the sampled tissue might not be entirely representative of the tumour and there is a lack of adequate numbers and follow-up to make clear conclusions as to a biomarker's prognostic potential. Formalin fixation and paraffin embedding (FFPE) is the clinical standard for preparing samples for histopathological assessment; this preserves tissue architecture and allows the storage of diagnostic and surplus tissue in archival banks. This resource represents a vast repository of tissue material with a long-term clinical follow-up. With the advent of high-throughput profiling technologies, there is a unique opportunity to screen and comprehensively evaluate many biomarkers. Such studies require the large sample numbers and outcome data which is a key feature of archival FFPE tissue. However, the process of FFPE induces chemical changes and degradation in tissue DNA, RNA and protein, which can make subsequent analysis unreliable. Recently, several technical advances have been made to overcome the degrading effects of FFPE. This review highlights the key advances that are beginning to allow the use of FFPE archives for molecular biomarker profiling.