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Comparative Pathology Core

Director: Amy Durham, MS, VMD, DACVP

The Comparative Pathology Core (CPC) is an established Shared Resource within the Department of Pathobiology at the University of Pennsylvania School of Veterinary Medicine (Penn Vet), and a fully integrated Shared Resource of the Abramson Cancer Center (ACC). The main objective of the CPC is to provide skillful interpretation of lesions in animals to fulfill the needs of ACC members using animal models of disease. Among the services provided are a full-service histology, clinical laboratory services for bloodwork and cytology, immunohistochemistry, digital pathology, comprehensive mouse phenotyping, slide evaluation and interpretation, study design consultation, necropsy training, and photomicroscopy. The IHC service (immunohistochemistry) utilizes an automated platform, multiplex immunofluorescence, and in situ hybridization; the CPC has numerous in-stock optimized antibodies, as well as the ability to work-up novel antibodies for investigators.

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Major Services

Services include access and utilization of three full-service laboratories: 1) histology; 2) clinical pathology; and 3) immunostaining (chromogenic immunohistochemistry [IHC]), in situ hybridization and immunofluorescence [IF]); digital pathology/whole slide digital scanning services with advanced image analysis and photomicroscopy; and study consultation, training and education, slide evaluation, and comprehensive mouse phenotyping and toxicologic studies with our board-certified veterinary pathologists. Critically, although other histology and immunostaining cores exist on Penn's campus, none includes the expertise of veterinary pathologists. Thus, the CPC is a unique, standalone Shared Resource that provides comprehensive "one-stop shopping" for its users and ensures project continuity, consistency, and rigor.

Based on ACC member feedback, the CPC prioritized the development of an immunostaining service for IHC, multiplex IF and other tissue-based molecular analysis. To accomplish this goal in 2017, the CPC acquired a fully automated BOND RXm staining platform. The platform allowed the rapid development and implementation of diverse protocols and techniques. The CPC now has a comprehensive service for advanced molecular labeling of animal tissues, including IHC, multiplex IF (up to four colors), lectin staining, and ISH utilizing the RNAScope® technology. This platform currently offers hundreds of validated protocols to label a variety of different sample types (e.g. paraffin-embedded or frozen tissue sections and cytological preparations) from a wide range of animal species. Particular emphasis is given to the development of comprehensive molecular panels in mouse tissues, including (i) distribution and functional status of immune cell populations; (ii) characterization of tumor microenvironment; (iii) validation of specific genetic systems, including reporter strategies (e.g. EGFP, tdTomato, FLAG-tag, Cre recombinase, Cas9, etc.); and (iv) biomarker discovery.

The creation of a digital pathology platform within the CPC was identified as another priority to increase capacity and accuracy of the existing pathology services. Dr. Durham was awarded an NIH Shared Instrumentation Grant (NIH S10 OD023465) for the acquisition of the Aperio VERSA digital pathology platform in 2018. The Aperio VERSA is a comprehensive digital pathology scanner, designed and developed to support the diverse imaging needs of both the diagnostic and research settings. The Aperio VERSA allows brightfield and fluorescence imaging of tissues configured to a sophisticated database management system for central storage, analysis, and sharing of images. The system is an integrated platform with several software modules for advanced imaging that offer state-of-the-art quantitative analysis. In collaboration with the Penn Vet Imaging Core, we are now developing protocols to exploit the full potential of the system.

Technologies and Major Equipment

Current equipment within the CPC includes: dual and multi-headed brightfield microscopes (Olympus BX40F, BX41, BX43F, BX53; Nikon Eclipse E400), fluorescence microscope (Nikon Eclipse E600 with DAPI, FITC, TRITC filter cubes), Olympus DP25 and DP22 digital cameras with Olympus cellSens digital imaging software and Adobe Photoshop for photomicroscopy, and a Canon EOS Rebel T3 digital camera for gross photographs. New major equipment for the immunostaining and digital pathology services are described above. In addition, the CPC has unfettered access to Penn Vet's comprehensive histology and clinical pathology laboratories.

For a full description of this service, please visit the Core's website: http://www.vet.upenn.edu/research/core-resources-facilities/comparative-pathology-core