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 4460 cases in 2012, producing about 33,615 immunostained slides for clinical service. The laboratory produced an additional 1500 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 2012 provided research support to multiple NCI and NIH laboratories, including the following NIH PIs. Dr. Elaine Jaffe (NCI) Dr. Wyndham Wilson (NCI) Dr. James Kochenderfer (NCI) Dr. Guiseppe Giaccone (NCI) Dr. Theo Heller (NIDDK) 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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC011087-06
Application #
8763761
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$1,778,625
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Legrand, Fanny; Tomasevic, Nenad; Simakova, Olga et al. (2014) The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders. J Allergy Clin Immunol 133:1439-47, 1447.e1-8
Liu, Yin; Jesus, Adriana A; Marrero, Bernadette et al. (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371:507-18
Park, Kang-Seo; Raffeld, Mark; Moon, Yong Wha et al. (2014) CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance. J Clin Invest 124:3003-15
Masaki, Taro; Wang, Yun; DiGiovanna, John J et al. (2014) High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients. Pigment Cell Melanoma Res 27:454-64
Glasker, Sven; Smith, Jonathan; Raffeld, Mark et al. (2014) VHL-deficient vasculogenesis in hemangioblastoma. Exp Mol Pathol 96:162-7
Liu, Qingyan; Salaverria, Itziar; Pittaluga, Stefania et al. (2013) Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma. Am J Surg Pathol 37:333-43
Huppmann, Alison R; Xi, Liqiang; Raffeld, Mark et al. (2013) Subcutaneous panniculitis-like T-cell lymphoma in the pediatric age group: a lymphoma of low malignant potential. Pediatr Blood Cancer 60:1165-70
Nicolae, Alina; Pittaluga, Stefania; Venkataraman, Girish et al. (2013) Peripheral T-cell lymphomas of follicular T-helper cell derivation with Hodgkin/Reed-Sternberg cells of B-cell lineage: both EBV-positive and EBV-negative variants exist. Am J Surg Pathol 37:816-26
Huppmann, Alison R; Roullet, Michele R; Raffeld, Mark et al. (2013) Angioimmunoblastic T-cell lymphoma partially obscured by an Epstein-Barr virus-negative clonal plasma cell proliferation. J Clin Oncol 31:e28-30
Herman, S E M; Sun, X; McAuley, E M et al. (2013) Modeling tumor-host interactions of chronic lymphocytic leukemia in xenografted mice to study tumor biology and evaluate targeted therapy. Leukemia 27:2311-21

Showing the most recent 10 out of 22 publications