Target validation, tissue microarrays

To further assess the clinical relevance of a particular cancer target it may be necessary to determine the association of the target protein levels, its localization, and/or its activity with a specific cancer type, stage, or prognosis. This will often require the generation and, most importantly, validation of robust antibodies for immunohistochemistry (IHC) to be used on tissue microarrays (TMAs) encompassing the relevant tumor types and, ideally, matched normal samples. 

Another method of validation is the use of standard samples from an approved source but such sources and tissue are not currently available. The use of consensus positive and negative tissue in the form of tissue microarrays is a possible substitute (Fitzgibbons et al, 2006). Alternatively, tissue samples from cases accessioned by your own laboratory known to harbor the target protein by non-IHC means can be used, but in all these situations it has to be remembered that there is no fixation or processing standard so that agreement between laboratories and between samples is subject to pre-analytical variables discussed previously. Clearly the ideal validation procedure would be against patient outcome but this is a costly exercise and often not practical as they require appropriate numbers of patients and a prospective study. 

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