"Liquid morphology": Immunochemical analysis of proteins extracted from formalin-fixed paraffin-embedded tissues: Combining proteomics with immunohistochemistry

Currently there are extensive efforts, national and international, to define the parameters affecting biomarker expression and stability to integrate this knowledge into diagnostic and therapeutic decisions, in effect to determine accurately and reliably which patients are likely to benefit from new targeted therapies, and which patients will not. Although challenging, efforts are being made to improve standardization of the preanalytical phase in hospitals. The introduction of guidelines for fixation and sample processing may improve molecular characterization of tissues to some degree. However, the authors believe that these approaches are likely to fall short because of the complexity of the problem, the diversity of personnel and institutions involved, and formidable issues of logistics and expense on a national or worldwide basis. Therefore, an alternative approach is proposed, specifically that the identification of biomarkers (quantifiable internal reference standards) that serve as indicators of tissue quality for both immunohistochemistry and protein microarrays, will improve the quality and reproducibility of in-vitro molecular diagnostic tests, and further may serve as a basis for precise quantification of analytes (proteins) in formalin-fixed paraffin-embedded tissues. Successful development and application of this approach would assure that protein biomarker profiles determined by proteomics or immunohistochemistry are related to the disease of the patient and not to vagaries of tissue processing.