Pathology Specimen Locator Core
The mission of the Pathology Specimen Locator Core is to facilitate Cancer Center member access to tissue. This is achieved through a web-based, integrated network of distributed, searchable databases that contain de-identified, coded, pathologic information on post-diagnostic, excess human materials (including frozen or paraffin-embedded tissues). Members may quickly retrieve information about aggregated tissue availability to determine the feasibility of a proposed study. Following IRB approval, they may discover, review, and request materials from suitable de-identified and coded cases. The standardized specimen core dataset includes age, gender, anatomic location, tissue type, and diagnoses.
Technical services include:
Query Design & Execution- Successful searches are the combination of sound database design and proper choice of search strategy. Careful selection of search terms depends on in depth understanding of the investigators' requests and how that translates into the terminology used in pathology reports. This helps to improve the yield of the searches and ensures more efficient selection of cases relevant to the specific inquiry. The query returns a list of cases appropriate for the study.
Block Retrieval- A single pathology case may generate more than 100 blocks. After the case list is generated, the PSL pathologist and staff review the pathology reports and perform slide reviews to identify appropriate blocks for the particular request. The pathology departments are then contacted by PSL staff, who requests the retrieval of the blocks.
Original H&E Slide Retrieval- When a clinical specimen is examined by a staff pathologist for diagnostic purposes, information critical to the PSL requestor may not find its way into the diagnostic report. This may be due to changes in clinical practice over time (e.g., differences in tumor classification, staging, or grading), or because the information needed by the requestor is not a standard component of the clinical report. As a result, the requested slides often need to be reviewed by the PSL team and participating pathologists to confirm the diagnosis or to provide the requested information. Certain studies also require the original study to be reviewed by independent observers.
Data Management- It is not uncommon for investigators to request additional materials from the same specimens for further testing. PSL manages and maintains information for each request to facilitate re-request. PSL can also provide de-identified clinical annotations linked to de-identified material, providing the user has the appropriate IRB approval.
Professional services include:
Facilitating Collaborations with Pathologists- Tissue-based research needs to be conducted with experts in histopathology to ensure proper interpretation of results. PSL has access to, and knowledge of, the expertise of pathologists affiliated with all the hospitals in DF/HCC and is thus well-positioned to connect investigators with experienced pathologists.
Block Selection By Slide Review- This service is usually provided by collaborating pathologists, but it is also available on a fee-for-service basis through the core.
Listed below are a few examples of how the core has contributed to various projects.
Profile (Personalized Cancer Medicine Partnership), B. RollinsDFCI
Profile, (formerly Personalized Cancer Medicine Partnership, PCMP), is a collaborative venture between two Harvard Medical School affiliated institutions - the Brigham and Women's Hospital (BWH) and the Dana-Farber Cancer Institute (DFCI). The mission of the Profile is to advance translational and personalized cancer medicine by implementing tumor genomic profiling on all cancer patients treated at these institutions.
OncoMap is the current platform for Profile. It was based on single-base extension chemistry and mass spectrometry from Sequenom and Center for Cancer Genome Discovery (CCGD) at DFCI. Oncomap test performed at Center for Advanced Molecular Diagnostics (CAMD) at BWH currently interrogates 471 specific mutations across 41 genes. OncoMap is structured as an IRB-approved research protocol and the test is offered to all patients of BWH and DFCI who have consented to get tested and to allow their test results to be deposited in a research database. Several platforms based on next-generation sequencing technologies are being evaluated at CCGD and CAMD and the plan is for Profile to actively engage in adopting new technologies and use them to generate a detailed profile of key "druggable" or otherwise "actionable" cancer genomic alterations in a CLIA-approved and "just-in-time" process to facilitate rapid clinical utilization. Profile has completed tumor genotyping using Oncomap for more than 1600 patients to date. The core has contributed with block identification, retrieval and slide preparation
High throughput interrogation of somatic mutations in high grade serous cancer of the ovary, W. HahnDFCI (Gynecologic Oncology Program). The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). The core has contributed with block identification, retrieval and slide preparation
Matulonis UA, Hirsch M, Palescandolo E, Kim E, Liu J, van Hummelen P, MacConaill L, Drapkin R, Hahn WC. PLoS One. 2011;6(9):e24433. Epub 2011 Sep 8.