The immunohistochemistry (IHC) laboratory is the primary CAP/CLIA certified laboratory performing tissue based immunohistochemical testing that subserves all LP diagnostic services. Immunohistochemical analysis of cancer and other diseases, is essential for modern surgical pathology diagnostics, and plays an increasingly critical role in identifying targets for molecular and immunologically targeted therapies. For example the identification of cancer-associated antigens MART-1, GP-100, CEA, CD19, CD20, CD52, CD2, CD25, CD20, P53, NY-ESO-1, HER-2, EGFR are necessary for enrollment into immune cell-based therapies developed by CCR Surgery Branch and/or antibody-based therapies developed by several other CCR Branches. Expression of a variety of tyrosine kinase receptors, including ERB2 (HER2), EGFR, and C-KIT predict or influence response to therapies targeting their signaling pathways. Expression of the transcription factor HIF-1alpha is required for enrollment in a phase 0 study of the topoisomerase inhibitor topotecan. In addition to performing this essential clinical service, the laboratory also provides research support to the larger NCI/NIH community and develops methods for interrogating novel targets using immunohistochemical methods. The immunohistochemistry core laboratory processed over 5000 cases in 2010, producing about 37,500 immunostained slides for clinical service. The laboratory produced an additional 600 slides in support of a variety of research projects, requested by both LP clinical researchers and NCI/NIH researchers from outside of LP. The laboratory tests include a panel of over 180 paraffin reactive antibodies, and 40 additional antibodies for frozen section studies. These include cell of origin diagnostic markers, cell signaling pathway activation markers, cell-type specific transcription factors, proliferation-related markers, and other prognostic markers. At any given time, the laboratory is developing or testing 5 or more novel antibodies for potential clinical or research use. Examples of new antibody tests developed by the service include type specific keratin antibodies, newly developed paraffin reactive CD markers including CD25, CD38, CD138, PD-1, CXCL13, tissue specific transcription factors and cell cycle regulators. Examples of the latter include MYF-4, CYCLIN D1, p27, HIF-1alpha, MITF, TFE3, FOXP3, OCT-2, OCT-4, BOB-1, PU-1, and several growth factor receptors such as c-KIT, EGRF, EGFRvIII and ERBB2. The laboratory is also developing assays to interrogate activated signaling pathway such as the PI3K/AKT and mTOR pathways. Specific targets being developed include PTEN, and phosphorylated forms of AKT, S6K, MTOR, and 4EBP1. The immunohistochemistry core laboratory supports translational research of both NCI and NIH researchers, and in 2010/11 provided research support to multiple NCI and NIH laboratories. Collaborations resulting in publications in 2010/11 are attached, and include studies with: Dr. Elaine Jaffe Dr. Wyndham Wilson Dr. James Kochenderfer Dr. Kenneth Kraemer Dr. Steven. Rosenberg Dr. Giovanni Melillo Among the many other NCI and NIH tenured investigators and clinicians that have utilized the laboratory's resources in the past year are: Dr. Guiseppe Giaccone (NCI) Dr. Steven Holland (NIAID) Dr. Su Young Kim (NCI) Dr. David Kleiner (NCI) Dr. Kenneth Kraemer (NCI) Dr. Giovanni Melillo (NCI-Frederick) Dr, Stefania Pittaluga (LP-NCI) Dr. Steven Rosenberg (NCI) Dr. Martha Quezado (NCI) Dr. Maria Tsokos (LP-NCI) Dr. Katherine Warren (NCI) Dr. Alan Wayne (NCI) Dr. Samuel Wells (NCI) Dr. Adrian Weistner (NHLBI)
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