The Development of Cross-Platform Quantitative Standards for Diagnostic Immunohis

DESCRIPTION (provided by applicant): Patient-specific therapies targeted to the phenotype of individual tumors represent the future of cancer treatment. The prototypes for this type of therapy are Herceptin and Tamoxifen, which are only given to patients e xpressing a particular level of HER2 and estrogen receptor (ER), respectively. It is likely that dozens of such therapies will be developed for a variety of tumors in the next decade. As with Herceptin and Tamoxifen, the diagnostic test for determining whi ch patients will be given what therapies will most likely involve immunohistochemical (IHC) staining of fixed tumor samples, since the routine HandE slide remains the standard for the anatomic diagnosis. Yet today's immunohistology labs have only the crude st of standards-usually a highly positive and a completely negative cell line or tissue control. The results from such stains are likely only accurate to at best one order of magnitude, even when newer automated quantitative stain readers are used. Further more, no attempt is made to assess the antigenic viability of patient samples. We believe that the future success of targeted therapy will be largely dependent upon the development of robust method of standardization for IHC that can be used to normalize r esults both across laboratories and across analysis platforms. Our goal is to develop a robust, adaptable immunohistochemical standard that can be processed alongside every patient tissue sample. This standard can then be used both to assess tissue antigen ic viability and to permit the quantification of biomarkers at the molecules-per-cell level. Public Health Relevance Statement: Patient-specific therapies represent the future of cancer treatment. Development of such therapies will require consiste nt and quantitative measures of patient tumors. Our goal is to develop robust, adaptable, and quantitative standards that can dramatically improve the analysis of patient tumors. These standards will help determine the most appropriate therapy for a patien t's tumor.