Toward Improving the Proteomic Analysis of Formalin-fixed, Paraffin-embedded Tissue

Carol B Fowler; Timothy J O'Leary; Jeffrey T Mason

Disclosures

Expert Rev Proteomics. 2013;10(4):389-400. 

In This Article

Formalin-fixed, Paraffin-embedded Tissue Proteomics: Current Status

Proteomics has emerged as a valuable translational research tool to identify differentially expressed proteins that can serve as biomarkers for specific human diseases.[1] Advances in proteomic technology allow thousands of proteins to be identified within fresh or frozen tissue samples.[2–5] However, fresh or frozen tissues to support longitudinal investigations of 10 years or more have very limited availability. This has frustrated proteomic studies of diseases that progress slowly or malignancies where the time between treatment and recurrence is long. A potential solution to this dilemma is the millions of archived formalin-fixed, paraffin-embedded (FFPE) tissues for which the clinical course of disease, response to therapy, recurrence and survival have been documented in their associated clinical records. Unfortunately, retrospective studies using FFPE tissues have been hindered by chemical modifications to proteins that occur during formaldehyde fixation and subsequent histological processing.[6,7] The most significant development in FFPE proteomics has come from the adaptation of heat-induced antigen retrieval methods, originally developed for immunohistochemistry (IHC), to the extraction of proteins from FFPE tissue.[2,8,9] Other recent important advances include the use of labeling reagents and label-free methods to improve the quantitative analysis of FFPE extracts[10,11] and protein mapping of intact FFPE tissue sections[12] by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). In this review, the authors will focus on recently developed methods that bring us closer to employing the advantages of FFPE tissue archives in the hunt for protein biomarkers of human disease.

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