Histopathology Facility

The Histopathology Facility (HF) provides Cancer Center members with technical processing of cells and tissues, gene expression in situ protein immunolocalization, pathology interpretation of microscopy findings, including target distribution and other metrics focused on particular cell/tissue compartments. We help establish and characterize animal models of human cancer and related diseases, as well as analysis of human tissue samples, including from clinical trials. Most projects involve animal models that require complex histological, immunohistochemical and/or cytological processing to determine morphological alterations, and to localize and quantify the expression of cancer-relevant gene products in tissue sections, including murine and human samples.

The Histopathology Facility (HF) supports two classes of analysis of tissue specimens: 1. classic and multi-chromatic histopathology, and 2 multiplex spatial and quantitative immunofluorescence:

1. Classic and multi-chromatic histopathology: The major objective of the animal/human research services of the Histopathology Facility (HF) is to facilitate research conducted by NCI/NIH-funded Cancer Center members by providing them with technical processing of cells and tissues as well as issuing reports of histopathological and immunohistochemical (IHC) /image analysis findings. Primary activities include:
   • Preparation of tissues for histopathological or cytological evaluation, i.e., embedding cells and tissues in paraffin, preparation of tissue sections, and staining. Preparation of frozen sections, histochemistry, IHC, including multi-chromatic IHC, and in situ hybridization. Provision of slide scanning and IHC image analysis as well as Laser Capture Microdissection (LCM).
   • Provision of interpretation and consultation on procedures, results and histopathological evaluations. The Facility also provides documentation on techniques and reports results. In addition, we document results using digital photography and work with Cancer Center members to devise custom-made approaches for projects as needed.
2. Multiplex spatial and quantitative immunofluorescence: Fully customizable signatures of multiple biomarkers (antibody based) design to gate on specific cell populations and query their spatial distributions with regards to other cells and tissue features. Capabilities include measuring tumor and stroma heterogeneity as well as dynamic modulation in response to experimental conditions using animal models as well as clinical samples. The multiplex approach allows for assessment of immune infiltrates, stroma staging, and tumor heterogeneity, antibody-based on protein expression patterns including subcellular distributions. Primary activities include:
   • Use of animal and human FFPE or frozen tissues, or cell blocks, including TMA formats, for staining with multiple (2 to >40) biomarkers via cycling multiplexed immunofluorescence (c-mIF). Services include multi-biomarker customizing, staining, and fluorescent-mIF tissue scanning, as well as image acquisition and pipeline processing for analysis of discrete regions of interest.
   • Gated immune-detection metrics (e.g. integrated intensity of targets detected, high versus low expresser populations, etc.). Spatial distribution analysis is powered by sophisticated AI platforms (e.g. VIOSOPHARM®). Data interpretation is assisted by an experienced pathologist who performs the diagnostic procedures and selects regions of interest. Data analyses are conducted in collaboration with users and specialists in the Bioinformatics and Biostatistics Facility to assure accurate and significant hypothesis-testing. Data can be integrated with architectural extracellular matrix (ECM) signatures acquired using multi photon microscopy within the same samples.