Accession of Clinically Annotated Pathology Specimens for Molecular Marker Research - Large numbers of clinically annotated specimens are required for the evaluation of markers and assays for clinical decision-making, but it is generally not possible to anticipate the specific needs of the research community. It is very costly to set up specimen banks for all the different possible needs. The Cancer Diagnosis Program (CDP) seeks to test a peer-to-peer informatics system to locate and retrieve specimens and pertinent clinical and outcome data on an as needed (just-in-time) basis from community health care settings. A system exists that has been shown to work in an academic setting, but much larger numbers of specimens are housed in the community setting. In addition Health Maintenance Organizations generally have both inpatient and outpatient records, and this can provide more complete treatment and recurrence information than that contained in tumor registries. CDP is supporting a program to develop and test an open-source, peer-to-peer computer program to identify pathologic specimens and associated clinical and outcome data in clinic and hospital settings. This program will be tested in 2-3 sites selected by CDP from members of the Cancer Research Network (funded by the NCI), in sites showing good quality, archived pathologic specimens suitable for molecular marker studies;and to have computerized medical record systems that are linked to the specimens. This program will initially test and adapt their previously developed de-identification protocol at the local sites, evaluating its performance on ever larger numbers of cases. Test retrieval queries will be constructed to include the identification of specimens from pathology reports and linkage to local clinical and outcome databases. Successive queries will be increasingly complex, including as many such databases as possible. Evaluation of the query results will be by manual inspection of data and pathology blocks using study and local personnel as appropriate. Tissue Microarrays - The Cancer Diagnosis Program (CDP) supports construction of statistically designed Tissue Microarrays (TMAs) using breast cancer tissue and clinical data. The TMAs will be used by breast cancer investigators to develop and validate prognostic and predictive diagnostic biomarkers. Archival, well annotated invasive breast carcinoma and DCIS pathology cases from the patient population in diverse geographic areas with 5-10 years of clinical follow data will be used for designing prognostic and progression TMAs with built in statistical significance. Clinical and outcome data fields associated with each case (patient) include: histological diagnosis, demographic data, extent of disease, treatment, follow-up, recurrence, survival and vital status. Each TMA requires several hundred breast cancer cases and needs to be selected from a much larger collection to avoid biases. Board certified pathologists need to select pathology blocks, cut slides from the blocks, perform QA/QC and mark the appropriate areas on the slides for coring and construction of the TMAs. Significant QA/QC also needs to be performed to assure that the clinical data associated with the specimens used in the TMAs is complete and accurate. The end results of this effort will be the delivery of quality assured tumor blocks with marked slides and complete and accurate data. Calibration of the BCR-ABL Assay for CML - The Cancer Diagnosis Program (CDP) supports the development and evaluation of molecular diagnostics for clinical practice. Acceptance by clinicians of the BCR-ABL assay for Chronic Myelogenous Leukemia (CML) is limited by the lack of standardization among the American laboratories that perform the assay. The assay uses quantitative RT-PCR, and despite being performed in CLIA-certified laboratories, one laboratory's results cannot be directly compared to anothers. Currently many American laboratories perform this assay using different protocols and different control genes. There are no commonly used calibrators to standardize the assay. The CDP is supporting this project to assess whether use of a uniform RNA calibrator improves standardization of this assay. The study sites must have a CLIA-certified laboratory that routinely performs the BCR-ABL assay according to their CLIA certified laboratory procedures and protocols, and the NCI will provide specially prepared samples including some duplicates and will provide calibrators.
