Formalin fixation in the '-omics' era: a primer for the surgeon-scientist

Formalin is the most commonly used tissue fixative worldwide. While it offers excellent morphological preservation for routine histology, it has detrimental effects on nucleic acids. Most studies of nucleic acids have therefore used fresh frozen tissue, the collection and storage of which is resource intensive. The ability to use modern genomic, transcriptomic and epigenomic methods with nucleic acids derived from formalin-fixed, paraffin-embedded (FFPE) tissues would allow enormous archives of routinely stored tissues (usually with well-annotated clinical data) to be used for translational research. This paper outlines the effects of formalin on nucleic acids, describes ways of minimizing nucleic acid degradation and optimizing extraction, and reviews recent studies that have used contemporary techniques to analyse FFPE-derived nucleic acids (with a focus on malignant tissue sources). Simple tips are also offered to ensure the utility of your institution's samples for future studies, and broadly applicable guidelines are listed for those contemplating their own study using FFPE-derived material.