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PD-L1 immunohistochemistry

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https://www.readbyqxmd.com/read/27913228/pd-l1-immunohistochemistry-assays-for-lung-cancer-results-from-phase-1-of-the-blueprint-pd-l1-ihc-assay-comparison-project
#1
Fred R Hirsch, Abigail McElhinny, Dave Stanforth, James Ranger-Moore, Malinka Jansson, Karina Kulangara, William Richardson, Penny Towne, Debra Hanks, Bharathi Vennapusa, Amita Mistry, Rasika Kalamegham, Steve Averbuch, James Novotny, Eric Rubin, Kenneth Emancipator, Ian McCaffery, J Andrew Williams, Jill Walker, John Longshore, Ming S Tsao, Keith M Kerr
BACKGROUND: The "Blueprint PD-L1 IHC Assay Comparison Project" is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials. METHODS: 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP 142 and SP 263) as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity...
November 29, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#2
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905110/distinct-molecular-landscapes-between-endometrioid-and-non-endometrioid-uterine-carcinomas
#3
Nathaniel L Jones, Joanne Xiu, Sudeshna Chatterjee-Paer, Alexandre Buckley de Meritens, William M Burke, Ana I Tergas, Jason D Wright, June Y Hou
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and non-endometrioid based on histo-pathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27889782/molecular-pathology-a-requirement-for-precision-medicine-in-cancer
#4
Manfred Dietel
The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27863197/programmed-death-ligand-1-expression-and-response-to-the-anti-programmed-death-1-antibody-pembrolizumab-in-melanoma
#5
Adil I Daud, Jedd D Wolchok, Caroline Robert, Wen-Jen Hwu, Jeffrey S Weber, Antoni Ribas, F Stephen Hodi, Anthony M Joshua, Richard Kefford, Peter Hersey, Richard Joseph, Tara C Gangadhar, Roxana Dronca, Amita Patnaik, Hassane Zarour, Charlotte Roach, Grant Toland, Jared K Lunceford, Xiaoyun Nicole Li, Kenneth Emancipator, Marisa Dolled-Filhart, S Peter Kang, Scot Ebbinghaus, Omid Hamid
Purpose Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27853827/increased-pd-l1-and-t-cell-infiltration-in-the-presence-of-hla-class-i-expression-in-metastatic-high-grade-osteosarcoma-a-rationale-for-t-cell-based-immunotherapy
#6
Yayan T Sundara, Marie Kostine, Arjen H G Cleven, Judith V M G Bovée, Marco W Schilham, Anne-Marie Cleton-Jansen
INTRODUCTION: Immunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas and relapses/metastases, as well as their changes during disease progression. MATERIALS AND METHODS: Tumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections...
November 16, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27844328/molecular-profiling-of-thymoma-and-thymic-carcinoma-genetic-differences-and-potential-novel-therapeutic-targets
#7
Franz Enkner, Bettina Pichlhöfer, Alexandru Teodor Zaharie, Milica Krunic, Tina Maria Holper, Stefan Janik, Bernhard Moser, Karin Schlangen, Barbara Neudert, Karin Walter, Brigitte Migschitz, Leonhard Müllauer
Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation...
November 14, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27843633/scoring-of-pd-l1-expression-intensity-on-pulmonary-adenocarcinomas-and-the-correlations-with-clinicopathological-factors
#8
Tomoyuki Igarashi, Koji Teramoto, Mitsuaki Ishida, Jun Hanaoka, Yataro Daigo
INTRODUCTION: The contribution of programmed cell death ligand-1 (PD-L1) immune checkpoint molecule toward progression of non-small cell lung cancer (NSCLC) has not yet been elucidated, in part, because of lack of a standardised method to evaluate PD-L1 expression. In this study, we developed a novel method for the evaluation of PD-L1 expression on NSCLC cells and examined its correlation with clinicopathological characteristics. METHODS: After immunohistochemical examination of PD-L1 expression for surgically resected pulmonary adenocarcinomas (n=106), based on the findings that PD-L1 are consistently expressed on alveolar macrophages, PD-L1 staining intensity of tumour cells was classified into four levels relative to PD-L1 staining intensity in alveolar macrophages; PD-L1 expression scores (range, 0-300) were semiquantitatively assessed...
2016: ESMO Open
https://www.readbyqxmd.com/read/27835597/pd-l1-promoter-methylation-is-a-prognostic-biomarker-for-biochemical-recurrence-free-survival-in-prostate-cancer-patients-following-radical-prostatectomy
#9
Heidrun Gevensleben, Emily Eva Holmes, Diane Goltz, Jörn Dietrich, Verena Sailer, Jörg Ellinger, Dimo Dietrich, Glen Kristiansen
BACKGROUND: The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa)...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834350/quantitative-and-pathologist-read-comparison-of-the-heterogeneity-of-programmed-death-ligand-1-pd-l1-expression-in-non-small-cell-lung-cancer
#10
Jamaal A Rehman, Gang Han, Daniel E Carvajal-Hausdorf, Brad E Wasserman, Vasiliki Pelekanou, Nikita L Mani, Joseph McLaughlin, Kurt A Schalper, David L Rimm
PD-L1 is expressed in a percentage of lung cancer patients and those patients show increased likelihood of response to PD-1 axis therapies. However, the methods and assays for the assessment of PD-L1 using immunohistochemistry are variable and PD-L1 expression appears to be highly heterogeneous. Here, we examine assay heterogeneity parameters toward the goal of determining variability of sampling and the variability due to pathologist-based reading of the immunohistochemistry slide. SP142, a rabbit monoclonal antibody, was used to detect PD-L1 by both chromogenic immunohistochemistry and quantitative immunofluorescence using a laboratory-derived test...
November 11, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27825291/programmed-death-ligand-1-expression-in-papillary-thyroid-cancer-and-its-correlation-with-clinicopathological-factors-and-recurrence
#11
Qinghai Ji, Rongliang Shi, Ning Qu, Tingxian Luo, Jun Xiang, Tian Liao, Guohua Sun, Yu Wang, Yu-Long Wang, Caiping Huang
Background Programmed death ligand 1 (PD-L1) expression has been reported in several malignancies, but the expression of PD-L1 in papillary thyroid cancer (PTC) is has been characterized rarely defined. The aim of this study was to assess the significance of PD-L1 expression and its associations with clinicopathological factors and disease outcome in PTC. Methods Immunohistochemistry staining was conducted retrospectively to evaluate the expression of PD-L1 in a total of 260 PTC tumors and corresponding non-tumor tissues...
November 8, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27816392/assessing-pdl-1-and-pd-1-in-non-small-cell-lung-cancer-a-novel-immunoscore-approach
#12
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee Khanehkenari, Samer Al-Saad, Sigurd M Hald, Sigve Andersen, Elin Richardsen, Nora Ness, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC...
October 5, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27815126/programmed-cell-death-ligand-pd-l1-expression-in-stage-ii-and-iii-lung-adenocarcinomas-and-nodal-metastases
#13
Hironori Uruga, Emine Bozkurtlar, Tiffany G Huynh, Alona Muzikansky, Yasushi Goto, Maria Gomez-Caraballo, Aaron N Hata, Justin F Gainor, Eugene J Mark, Jeffrey A Engelman, Michael D Lanuti, Mari Mino-Kenudson
INTRODUCTION: PD-L1 expression by immunohistochemistry (IHC) may serve as a predictive biomarker for anti-PD-1/PD-L1 therapies; however, little is known about intertumoral heterogeneity of PD-L1 expression by IHC in lung adenocarcinomas (ADC), and there have been conflicting results on the prognostic role of PD-L1 expression in ADC. METHODS: PD-L1expression was evaluated in resected stage II and III ADC using various cutoffs, and was correlated with clinicopathologic parameters and survival...
November 1, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27807760/programmed-death-ligand-1-expression-microsatellite-instability-epstein-barr-virus-and-human-papillomavirus-in-nasopharyngeal-carcinomas-of-patients-from-the-philippines
#14
Ann Margaret V Chang, Simion I Chiosea, Alexey Altman, Hester A Pagdanganan, Changqing Ma
Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry...
November 2, 2016: Head and Neck Pathology
https://www.readbyqxmd.com/read/27801734/pd-l1-expression-in-carcinosarcomas-of-the-gynecologic-tract-a-potentially-actionable-biomarker
#15
Andre Pinto, Nicholas Mackrides, Mehrdad Nadji
BACKGROUND: Carcinosarcomas of the gynecologic tract, also known as malignant mixed Müllerian tumors, are aggressive neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. In fact, there are currently no consensus guidelines for the treatment of these neoplasms and the search for targetable biomarkers has not been successful so far. Programmed death-ligand 1 (PD-L1) has emerged as a potential target for therapeutics in a number of malignant tumors, including melanoma, lung, and colorectal cancer...
October 31, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27797936/il-6-and-pd-l1-antibody-blockade-combination-therapy-reduces-tumour-progression-in-murine-models-of-pancreatic-cancer
#16
Thomas A Mace, Reena Shakya, Jason R Pitarresi, Benjamin Swanson, Christopher W McQuinn, Shannon Loftus, Emily Nordquist, Zobeida Cruz-Monserrate, Lianbo Yu, Gregory Young, Xiaoling Zhong, Teresa A Zimmers, Michael C Ostrowski, Thomas Ludwig, Mark Bloomston, Tanios Bekaii-Saab, Gregory B Lesinski
OBJECTIVE: Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. DESIGN: Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively...
October 21, 2016: Gut
https://www.readbyqxmd.com/read/27788043/development-of-a-prototype-immunohistochemistry-assay-to-measure-programmed-death-ligand-1-expression-in-tumor-tissue
#17
Marisa Dolled-Filhart, Darren Locke, Tiffany Murphy, Frank Lynch, Jennifer H Yearley, Dennis Frisman, Robert Pierce, Russell Weiner, Dianna Wu, Kenneth Emancipator
CONTEXT: - With the abundance of therapeutics targeted against programmed death receptor-1 and its ligand (PD-L1) that are currently approved or in clinical development, there is interest in identifying those patients most likely to respond to these drugs. Expression of PD-L1 may be an indicator of an initial and robust inflammatory response to the presence of tumor cells. Therefore, tumors that express PD-L1 may be the most likely to respond to therapies that interrupt the negative feedback mechanism that leads to PD-L1 upregulation...
November 2016: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/27784882/induction-of-patient-derived-xenograft-formation-and-clinical-significance-of-programmed-cell-death-ligand-1-pd-l1-in-lung-cancer-patients
#18
Yuanyuan Ma, Panpan Zhang, Guo An, Xiaolong Zhang, Liyi Zhang, Jiahui Si, Jianzhi Zhang, Yue Yang
BACKGROUND The immune checkpoint of programmed cell death ligand 1 (PD-L1) commonly expressed in solid cancers, and the blockade of this molecule show promising results in advanced cancers, including lung cancer. The relevance of PD-L1 to patient-derived xenograft (PDX) formation and clinicopathological characteristics in early stage lung cancer have not been fully elucidated. MATERIAL AND METHODS Cell counting kit-8 and flow cytometry were carried out to examine proliferation and apoptosis in PC9 and H520 cells transfected with siRNAs...
October 27, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27777774/5-fluorouracil-upregulates-cell-surface-b7-h1-pd-l1-expression-in-gastrointestinal-cancers
#19
Lauren Van Der Kraak, Gaurav Goel, Krishnaveni Ramanan, Christof Kaltenmeier, Lin Zhang, Daniel P Normolle, Gordon J Freeman, Daolin Tang, Katie S Nason, Jon M Davison, James D Luketich, Rajeev Dhupar, Michael T Lotze
BACKGROUND: Resistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, also known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed in several human cancers. Interaction of B7-H1 with programmed death 1 (PD-1) prevents T-cell activation and proliferation, sequestering the T-cell receptor from the cell membrane, inducing T-cell apoptosis, thereby leading to cancer immunoresistance. B7-H1 upregulation contributes to chemoresistance in several types of cancer, but little is known with respect to changes associated with 5-fluorouracil (5-FU) or gastrointestinal cancers...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27776338/pd-l1-expression-in-tonsillar-cancer-is-associated-with-human-papillomavirus-positivity-and-improved-survival-implications-for-anti-pd1-clinical-trials
#20
Angela M Hong, Ricardo E Vilain, Sarah Romanes, Jean Yang, Elizabeth Smith, Deanna Jones, Richard A Scolyer, C Soon Lee, Mei Zhang, Barbara Rose
In this study, we examined PD-L1 expression by immunohistochemistry in 99 patients with tonsillar cancer and known human papillomavirus (HPV) status to assess its clinical significance. We showed that the pattern of PD-L1 expression is strongly related to HPV status. The PD-L1 positivity rate was 83.3% in HPV-positive cases and 56.9% in HPV-negative cases (p < 0.05). Patients with HPV-positive/PD-L1-positive cancer had significantly better event free survival and overall survival compared with patients with HPV-negative/PD-L1-negative cancer...
October 20, 2016: Oncotarget
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