Immunohistochemistry Core Laboratory

免疫组化核心实验室

• 批准号: 8763761
• 负责人: Mark Raffeld
• 金额: $ 177.86万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763761
• 关键词: Antibodies; Biological Assay; C-KIT Gene; CCR; CD19 gene; CDW52 gene; CTAG1 gene; CXCL13 gene; Cell Cycle; Cell Therapy; Cells; Clinical; Clinical Services; Communities; Diagnostic; Diagnostic Services; Disease; ERBB2 gene; Enrollment; Epidermal Growth Factor Receptor; Frozen Sections; Growth Factor Receptors; HIF1A gene; IL2RA gene; Immune; Immunohistochemistry; Keratin; Laboratories; MART-1 Tumor Antigen; MS4A1 gene; Malignant Neoplasms; Methods; Molecular Target; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Diabetes and Digestive and Kidney Diseases; Operative Surgical Procedures; PI3K/AKT; PTEN gene; Paraffin; Pathway interactions; Phase; Play; Process; Prognostic Marker; Proto-Oncogene Proteins c-akt; Receptor Protein-Tyrosine Kinases; Research; Research Personnel; Research Project Grants; Research Support; Role; Services; Signal Pathway; Signal Transduction; Slide; Surgical Pathology; TFE3 gene; TP53 gene; Testing; Time; Tissues; Topoisomerase Inhibitors; Topotecan; Translational Research; United States National Institutes of Health; base; cell type; epidermal growth factor receptor VIII; human FRAP1 protein; novel; response; therapy development; transcription factor

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)

免疫组织化学（IHC）实验室是基于组织基于组织的免疫组织化学测试的主要CAP/CLIA认证的实验室，可实现所有LP诊断服务。对癌症和其他疾病的免疫组织化学分析对于现代手术病理学诊断至关重要，并且在鉴定分子和免疫靶向疗法的靶标方面起着越来越重要的作用。例如，鉴定与癌症相关的抗原MART-1，GP-100，CEA，CD19，CD20，CD20，CD2，CD2，CD25，CD20，CD20，p53，NY-ESO-1，HER-2，EGFR，对于通过CCR手术分支和/或抗体基于/或抗体基于/或抗体基于CRCR开发的免疫细胞疗法是必不可少的。各种酪氨酸激酶受体的表达，包括ERB2（HER2），EGFR和C-KIT预测或影响对靶向其信号通路的疗法的反应。转录因子HIF-1Alpha的表达是在拓扑异构酶抑制剂拓扑转基因的0期研究中需要的。除了执行这项基本的临床服务外，实验室还为更大的NCI/NIH社区提供研究支持，并开发了使用免疫组织化学方法询问新目标的方法。免疫组织化学核心实验室在2012年处理了4460例以上的病例，可为临床服务产生约33,615个免疫染色幻灯片。 LP临床研究人员和NCI/NIH的研究人员都要求从LP外部使用LP临床研究人员和NCI/NIH的研究人员要求，该实验室还制作了1500张幻灯片，以支持各种研究项目。实验室测试包括一个超过180种石蜡反应性抗体的面板，以及40种用于冷冻切片研究的其他抗体。其中包括原点诊断标记，细胞信号通路激活标记，细胞类型特异性转录因子，与增殖相关的标记和其他预后标记。在任何给定时间，实验室正在开发或测试5种或更多新型抗体，用于潜在的临床或研究用途。该服务开发的新抗体测试的实例包括特定的角蛋白抗体，新开发的石蜡反应性CD标记，包括CD25，CD38，CD138，PD-1，CXCL13，组织特定的转录因子和细胞周期调节剂。后者的例子包括MyF-4，Cyclin D1，P27，HIF-1Alpha，Mitf，TFE3，Foxp3，Oct-2，Oct-2，Oct-4，Bob-1，PU-1和几种生长因子受体，例如C-KIT，EGRF，EGRF，EGFRVIII和ERBB2。该实验室还正在开发测定法，以询问激活的信号通路，例如PI3K/AKT和MTOR途径。开发的特定靶标包括Akt，S6K，MTOR和4EBP1的PTEN和磷酸化形式。免疫组织化学核心实验室支持NCI和NIH研究人员的转化研究，并在2012年为包括以下NIH PIS在内的多个NCI和NIH实验室提供了研究支持。 Elaine Jaffe博士（NCI）Wyndham Wilson博士（NCI）博士James Kochenderfer博士（NCI）Guiseppe Giaccone博士（NCI） （NCI-Frederick）博士，Stefania Pittaluga（LP-NCI）Steven Rosenberg博士（NCI）Martha Quezado博士（NCI）Maria Tsokos博士（LP-NCI）