The objective of this proposal is to develop and validate synthetic calibration standards for clinical immunohistochemical (IHC) assays. IHC assays are the standard of care in cancer diagnosis and surgical pathology, but they suffer from a serious problem with inherent variability. Accuracy in testing is hampered by the lack of standardized test materials, which prevents the establishment of uniform and quantitative methods and diagnostic criteria. Most clinical IHC assays detect cellular antigens that are expensive to produce for use as controls. CytoLogic solved this problem by developing phage display methods to produce peptide mimics of cellular antigens, which serve as surrogates for native antigens. Now, we propose to produce, precise, quantitative IHC calibration standards for use with microscope-based quantitative imaging systems. One set of on-slide calibrators will control for analytic variability, which can result from reagent degradation or assay errors. A second set of processing calibrators will control for pre-analytic variability, which is associated with tissue fixation or antigen retrieval. This work will lead to a Phase II proposal for clinical validation trials for the IHC calibration standards. Development of uniform IHC calibration standards for important pharmacodiagnostic analytes will elevate quality control in the histopathology laboratory to the level of other clinical laboratories that produce quantitative data.
The technology described in this proposal will provide the first commercially produced quantitative standard for quality control of clinical immunohistochemical assays. Standards are important to identify sources of assay variability and to ensure that patient test results are accurate and reproducible regardless of which laboratory performs them.
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