Synthetic Calibrators for Immunohistochemical Assays

描述(由申请人提供)： 这项第二阶段拨款提案的广泛和长期目标是提高乳腺癌诊断的准确性。具体地说，这项第二阶段拨款提案是用于一项新技术的临床测试，该技术将促进Her2量化的国家标准。这对于适当的病人管理是很重要的。大量研究表明，用免疫组织化学方法对Her2进行临床实验室检测是错误的。我们用于开发分析控制的技术将成为首个用于细胞分析物的国家标准和可重复性的测试材料，例如在组织活检中测量的Her2。 在这个第二阶段的提案中，我们将通过五个具体目标将Her2 Analyte Controls引入临床。在具体目标1中，我们在第一阶段可行性工作的基础上完成了Her2分析控制，以便它们将适用于所有FDA批准的Her2测试。在目标2中，我们完成了一个简单、低成本的显微镜载玻片扫描仪，实验室将使用它来量化对照。然后，我们将根据细胞Her2的特定摩尔浓度(特定目标3)来校准我们的Analyte控制。通过这种方式，Analyte Controls技术可以作为一种工具，以摩尔浓度表示患者的结果，从而促进实验室间的标准化，这是目前无法实现的。具体目标4和5涉及临床测试。首先，我们将调查全国临床组织病理学实验室样本(特定目标4)，以确定Her2免疫染色敏感性的平均值和标准差。为此，我们招募了一家全国性的水平测试机构，该机构将向所有参与者发送我们的分析控制。最后，我们将在新英格兰医院的五个临床组织病理学实验室测试Analyte Controls，为期六个月。我们预计，这些数据最终将用于我们的商业合作伙伴提交给FDA的报告，以及开发新的癌症分析物组织量化国家标准。

DESCRIPTION (provided by applicant): The broad, long-term objective of this Phase II grant proposal is to improve accuracy of breast cancer diagnosis. Specifically, this Phase II grant proposal is for clinical testing of a new technology that will promote national standardization of Her2 quantification. This is of importance for proper patient management. Numerous studies have shown that clinical laboratory measurement of Her2 by immunohistochemistry is fraught with errors. Our technology for the development of Analyte Controls will be the first nationally standardized and reproducible test material for cellular analytes, such as Her2, measured in tissue biopsies. In this Phase II proposal, we will bring Her2 Analyte Controls to the clinic, through five Specific Aims. In Specific Aim 1, we build on the Phase I feasibility work by finishing the Her2 Analyte Controls so that they will be applicable for all FDA-approved Her2 tests. In Aim 2, we finish a simple, low-cost microscope slide scanner that laboratories will use to quantify the controls. We then will calibrate our Analyte Controls to specific molar concentrations of cellular Her2 (Specific Aim 3). In this way, the Analyte Controls technology can foster inter-laboratory standardization by serving as a tool for expressing patient results in tems of molar concentration, something that is not presently possible. Specific Aims 4 and 5 involve clinical testing. First, we will survey a national sample of clinical histopathology laboratories (Specific Aim 4), to identify the mean and standard deviation of Her2 immunostaining sensitivity. To do this, we have recruited the involvement of a national proficiency testing agency, which will send out our Analyte Controls to all of their participants. Lastly, we will test the Analyte Controls in five New England hospital clinical histopathology laboratories, for a period of six months. We expect that this data will ultimately be used for FDA submission by our commercial partner and the development of new national standards for tissue quantification of cancer analytes.