YEARS

-

AUTHORS

Mark Raffeld

TITLE

Immunohistochemistry Core Laboratory

ABSTRACT

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 ERBB2 (HER2), EGFR, and C-KIT predict or influence response to therapies targeting their signaling pathways. In addition to performing this essential clinical service, the laboratory also provides research support to both Laboratory of Pathology clinical researchers and to the larger NCI/NIH community developing antibody based assays for interrogating novel targets using immunohistochemical methods. The immunohistochemistry core laboratory processed over 4200 cases in 2014, producing over 28,000 immunostained slides for clinical service. The laboratory produced an additional 1000 slides in support of a variety of research projects, requested by both LP clinical researchers and NCI/NIH researchers from outside of the Laboratory of Pathology. 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, PD-L1, 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, mTOR, and JAK/STAT pathways. Specific targets being developed include PTEN, and phosphorylated forms of AKT, S6K, MTOR, 4EBP1, STAT3, and STAT5b. Additional targets include mutated forms of EGFR (L858R, and EGFR exon 19 deletion variants), BRAF (V600E), and IDH1 (R132H) and a more a sensitive ALK antibody that can detect EL4-ALK fusion protein found in lung cancer. The immunohistochemistry core laboratory supports translational research of both NCI and NIH researchers, and in 2013 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. Theo Heller (NIDDK), Dr. Steven Holland (NIAID), Dr. David Kleiner (NCI), Dr. Kenneth Kraemer (NCI), Dr, Stefania Pittaluga (LP-NCI), Dr. Steven Rosenberg (NCI), Dr. Martha Quezado (NCI), Dr. Tim Greten, Dr. Katherine Warren (NCI), Dr. Adrian Weistner (NHLBI), Dr. Raphaela Goldbach-Mansky.

FUNDED PUBLICATIONS

  • Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1.
  • Therapeutic vulnerability of an in vivo model of alveolar soft part sarcoma (ASPS) to antiangiogenic therapy.
  • Chronic active Epstein-Barr virus infection: a novel cause of lymphocytic variant hypereosinophilic syndrome.
  • NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis.
  • Bone marrow findings in HIV-positive patients with Kaposi sarcoma herpesvirus-associated multicentric Castleman disease.
  • Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments.
  • Modeling tumor-host interactions of chronic lymphocytic leukemia in xenografted mice to study tumor biology and evaluate targeted therapy.
  • Protracted haemangioblastic proliferation and differentiation in von Hippel-Lindau disease.
  • Composite B-cell and T-cell lineage post-transplant lymphoproliferative disorder of the lung with unusual cutaneous manifestations of mycosis fungoides.
  • Activated STING in a vascular and pulmonary syndrome.
  • Gene expression profiling of alveolar soft-part sarcoma (ASPS).
  • Increased CD5-positive polyclonal B cells in Castleman disease: a diagnostic pitfall.
  • Heat-induced antigen retrieval for immunohistochemical reactions in routinely processed paraffin sections.
  • EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell malignancies.
  • Immunohistochemical discrimination between the ASPL-TFE3 fusion proteins of alveolar soft part sarcoma.
  • Avidin-biotin labeling of cellular antigens in cryostat-sectioned tissue.
  • Adult T-cell leukemia/lymphoma with Epstein-Barr virus-positive Hodgkin-like cells.
  • Menin immunoreactivity in secretory granules of human pancreatic islet cells.
  • Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma.
  • Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor.
  • Gene expression profiling of alveolar soft-part sarcoma (ASPS)
  • Genetic diversity in melanoma metastases from a patient with xeroderma pigmentosum.
  • Marginal zone lymphomas involving meningeal dura: possible link to IgG4-related diseases.
  • High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients.
  • Multiple antigen immunostaining procedures.
  • Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations.
  • Coexisting and clonally identical classic hodgkin lymphoma and nodular lymphocyte predominant hodgkin lymphoma.
  • Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone.
  • A Hereditary Form of Small Intestinal Carcinoid Associated With a Germline Mutation in Inositol Polyphosphate Multikinase.
  • The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders.
  • Angioimmunoblastic T-cell lymphoma partially obscured by an Epstein-Barr virus-negative clonal plasma cell proliferation.
  • Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR.
  • Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications.
  • Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR
  • Nodal and extranodal plasmacytomas expressing immunoglobulin a: an indolent lymphoproliferative disorder with a low risk of clinical progression.
  • Nodal involvement by cutaneous CD30-positive T-cell lymphoma mimicking classical Hodgkin lymphoma.
  • Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival.
  • Progression of epididymal maldevelopment into hamartoma-like neoplasia in VHL disease.
  • Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1α in advanced solid tumors.
  • Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases
  • Modeling tumor–host interactions of chronic lymphocytic leukemia in xenografted mice to study tumor biology and evaluate targeted therapy
  • Differential expression of IRF8 in subsets of macrophages and dendritic cells and effects of IRF8 deficiency on splenic B cell and macrophage compartments
  • NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis
  • Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma.
  • Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers.
  • B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma.
  • Marginal zone lymphomas involving meningeal dura: possible link to IgG4-related diseases
  • Gall bladder and extrahepatic bile duct lymphomas: clinicopathological observations and biological implications.
  • Peripheral T-cell lymphoma with aberrant expression of CD30, CD15, and CD20.
  • Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder.
  • Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19.
  • 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.
  • Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas.
  • VHL-deficient vasculogenesis in hemangioblastoma.
  • The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia.
  • Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition.
  • CD15-expressing nodular lymphocyte-predominant Hodgkin lymphoma.
  • Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma.
  • Subcutaneous panniculitis-like T-cell lymphoma in the pediatric age group: a lymphoma of low malignant potential.
  • Amelanotic melanoma in a New Zealand White Rabbit (Oryctolagus cuniculus).
  • Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases.
  • Metachronous EBV-associated B-cell and T-cell posttransplant lymphoproliferative disorders in a heart transplant recipient.
  • Nonhepatosplenic γδ T-cell lymphomas represent a spectrum of aggressive cytotoxic T-cell lymphomas with a mainly extranodal presentation.
  • Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations
  • EBV positive mucocutaneous ulcer--a study of 26 cases associated with various sources of immunosuppression.
  • A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response.
  • CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance.
  • Successful treatment of a patient with Epstein-Barr virus-positive B-cell lymphoproliferative disorder resembling post-transplant lymphoproliferative disorder using single-agent rituximab.
  • Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma.
  • How to use: Click on a object to move its position. Double click to open its homepage. Right click to preview its contents.

    Download the RDF metadata as:   json-ld nt turtle xml License info


    83 TRIPLES      14 PREDICATES      84 URIs      7 LITERALS

    Subject Predicate Object
    1 grants:006251a2e1ea3563815a13cfad66cee2 sg:abstract 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 ERBB2 (HER2), EGFR, and C-KIT predict or influence response to therapies targeting their signaling pathways. In addition to performing this essential clinical service, the laboratory also provides research support to both Laboratory of Pathology clinical researchers and to the larger NCI/NIH community developing antibody based assays for interrogating novel targets using immunohistochemical methods. The immunohistochemistry core laboratory processed over 4200 cases in 2014, producing over 28,000 immunostained slides for clinical service. The laboratory produced an additional 1000 slides in support of a variety of research projects, requested by both LP clinical researchers and NCI/NIH researchers from outside of the Laboratory of Pathology. 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, PD-L1, 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, mTOR, and JAK/STAT pathways. Specific targets being developed include PTEN, and phosphorylated forms of AKT, S6K, MTOR, 4EBP1, STAT3, and STAT5b. Additional targets include mutated forms of EGFR (L858R, and EGFR exon 19 deletion variants), BRAF (V600E), and IDH1 (R132H) and a more a sensitive ALK antibody that can detect EL4-ALK fusion protein found in lung cancer. The immunohistochemistry core laboratory supports translational research of both NCI and NIH researchers, and in 2013 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. Theo Heller (NIDDK), Dr. Steven Holland (NIAID), Dr. David Kleiner (NCI), Dr. Kenneth Kraemer (NCI), Dr, Stefania Pittaluga (LP-NCI), Dr. Steven Rosenberg (NCI), Dr. Martha Quezado (NCI), Dr. Tim Greten, Dr. Katherine Warren (NCI), Dr. Adrian Weistner (NHLBI), Dr. Raphaela Goldbach-Mansky.
    2 sg:fundingAmount 7385149.0
    3 sg:fundingCurrency USD
    4 sg:hasContribution contributions:678ed524d6243d202823e0979b9724f9
    5 sg:hasFieldOfResearchCode anzsrc-for:11
    6 anzsrc-for:1112
    7 sg:hasFundedPublication articles:0201066d5ea28558df9700479b03ed3b
    8 articles:040875b1d0d81628d257e1a9fc9de964
    9 articles:04f89829f7094f556a1762af61fc955e
    10 articles:0565854c1f39b706f1b46b6f3955461f
    11 articles:12aead22b48219f054d890dce0dc7cae
    12 articles:1aad9f24006216c66bfbe086ad331efd
    13 articles:1b3501e2a201d8d3f42e07e68cdf66fc
    14 articles:23bbf6a0a367084a3f97437d23612d3a
    15 articles:2a34e2d1b5f839a3df009c04e6d298cd
    16 articles:2c5da19c9a0adb9d82625e3a6388b5e4
    17 articles:2d95bcede80bc77f5d2ee4cd7a0502e8
    18 articles:3b7ad03867445dda8119ad84905d74e6
    19 articles:3c20ccdd7f88de7f37b95260c1db1568
    20 articles:3e19c8221eb24082365f836812aada8a
    21 articles:404429252d702ad7252fdc90c362b483
    22 articles:43bee1361f7ddaba42ea32fdde28a993
    23 articles:44bbb3efc49934f84b632037b5d78f4b
    24 articles:44c5dc2476e63a1882fd9e5316a1670d
    25 articles:44c68c697a1604e544c31a5445066d9b
    26 articles:50384c9aa503287f1957860fdd4a4adc
    27 articles:580ac72e60f0194c319d2481fa26a4b5
    28 articles:5a83522413ac66a3d4dd54e1639a8758
    29 articles:5bba7fe80a8f12c5c57c36091e56a752
    30 articles:5dc275162ea85819e89531286b9ea025
    31 articles:5f838fd86a6a24b1f01d3b056e1dc2b2
    32 articles:654e06f08e514295ab4a46ed419a9823
    33 articles:65c10c253ae9b356dbc70df298600862
    34 articles:673bbe7f674346d4f158bcb6e2617756
    35 articles:6c28b0d1f56fcb8696046528a2b1c799
    36 articles:708f62b1bc46c93cf9fd5450f12666c7
    37 articles:73f0455f523b74a7542b1e88a01173cd
    38 articles:74bfd630b99e44d51a12ef6d53c05712
    39 articles:75b973cd2c79aeb7aba4bb520b7721e5
    40 articles:787db10c0c8e65852599f68bde0ef8dc
    41 articles:7bfc96a230b10d830e3a681c230b48f9
    42 articles:7e18da164615724e3a71e354bda7e855
    43 articles:7ecec89407d0d1a2ab7a5d2bb868348c
    44 articles:7ff73911b106787c511ab6937e1468b0
    45 articles:839c478a47da7d5588e1e241ad635989
    46 articles:8ab20ce34ab6bd6a5140e842ed0bdc69
    47 articles:8b255d1ad50e2e96cd06d9d9ec683119
    48 articles:8bbe674ca1e714dd67fbe6b5c21d5826
    49 articles:8dbb00417949f922e848321b5c9db10f
    50 articles:9310f27ce62f69939efe9d8cacd42856
    51 articles:939f377456acfd0ef443b56539026dcf
    52 articles:94feb9049556180dd317f60dbb62e7ac
    53 articles:a289c7abf5188142c58787ec1863efc8
    54 articles:a8e19de3de5c35cce20b75cfed1aa505
    55 articles:ad879136bafbee639e979babb0e9d52e
    56 articles:adf3a680223eb0842bf7174b44afb895
    57 articles:b6a31f5808258a1f5915b8cd60c433c8
    58 articles:b6c311f7c27e4938ac07e67ef40c3349
    59 articles:bbac8164fcf32440874fe4f8f9764cb1
    60 articles:c024478f6603b696bedc54b7d6c24155
    61 articles:c29359aba31bcd746a3b2d54fa7b69d8
    62 articles:cb049b97d456f9eaf741b5c96e90818f
    63 articles:d53ef4d0140c9b5b168175d3f4f10c98
    64 articles:d54a3ef4443799c5873ac7d793d91629
    65 articles:d9c99f9603939061e8c2ce9058463bbf
    66 articles:e4e4b36936fbe2b024913e5deed98b28
    67 articles:e77b7a43b428b6af1e0933141ea197e9
    68 articles:e841e99ed2c6cb52238ffef20961c57a
    69 articles:e8715a2b3c70cc7a0f89e1c18a394c85
    70 articles:e87f326de169ad3e592d66321e91f9e0
    71 articles:ef0d47ad26db39c92363f30129ac7140
    72 articles:f1ffef229e158a3c5a868177ad3dcf9a
    73 articles:f3ea4c5445996f60015f30dbe9040181
    74 articles:f7e3c9994f5d823ad7071a93f721e93c
    75 articles:fd60bdcc67e5bad013b607b173f5d514
    76 sg:hasFundingOrganization grid-institutes:grid.48336.3a
    77 sg:language English
    78 sg:license http://scigraph.springernature.com/explorer/license/
    79 sg:scigraphId 006251a2e1ea3563815a13cfad66cee2
    80 sg:title Immunohistochemistry Core Laboratory
    81 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=9154320
    82 rdf:type sg:Grant
    83 rdfs:label Grant: Immunohistochemistry Core Laboratory
    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular JSON format for linked data.

    curl -H 'Accept: application/ld+json' 'http://scigraph.springernature.com/things/grants/006251a2e1ea3563815a13cfad66cee2'

    N-Triples is a line-based linked data format ideal for batch operations .

    curl -H 'Accept: application/n-triples' 'http://scigraph.springernature.com/things/grants/006251a2e1ea3563815a13cfad66cee2'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'http://scigraph.springernature.com/things/grants/006251a2e1ea3563815a13cfad66cee2'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'http://scigraph.springernature.com/things/grants/006251a2e1ea3563815a13cfad66cee2'






    Preview window. Press ESC to close (or click here)


    ...