Synthetic calibrators for immunohistochemical assays

本提案的目的是开发和验证临床免疫组织化学（IHC）测定的合成校准标准品。IHC测定是癌症诊断和手术病理学中的护理标准，但它们存在固有可变性的严重问题。由于缺乏标准化的测试材料，无法建立统一的定量方法和诊断标准，因此测试的准确性受到影响。大多数临床IHC测定检测细胞抗原，这些细胞抗原的生产成本很高，用作对照。CytoLogic通过开发噬菌体展示方法来产生细胞抗原的肽模拟物，作为天然抗原的替代物，解决了这个问题。现在，我们建议生产精确的定量IHC校准标准品，用于基于显微镜的定量成像系统。一组载玻片校准品将控制分析变异性，这可能由试剂降解或测定错误引起。第二组处理校准品将控制与组织固定或抗原修复相关的分析前变异性。这项工作将导致第二阶段的建议，临床验证试验的IHC校准标准。为重要的药物诊断分析物开发统一的IHC校准标准品将把组织病理学实验室的质量控制提升到产生定量数据的其他临床实验室的水平。拟议的商业应用：本提案中描述的技术将为临床免疫组织化学测定的质量控制提供第一个商业化生产的定量标准。标准品对于确定检测变异性的来源以及确保患者检测结果准确且可重现（无论由哪个实验室执行）非常重要。

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. PROPOSED COMMERCIAL APPLICATIONS: 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.