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A Arfaoui Toumi, A Blel, R Aloui, H Zaibi, M Ksentinini, M S Boudaya, N Znaidi, Y Zidi, H Aouina, S Rammeh Rommani
BACKGROUND: Despite recent advances, non-small cell lung cancer carries a grim prognosis. For appropriate treatment selection, the updated guidelines recommend broad molecular profiling for all patients with pulmonary adenocarcinoma. Precise histological subtyping and targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) testing are mandatory. METHODS: Herein, we assessed the EGFR mutation status of 26 formalin fixed-paraffin embedded (FFPE) samples of lung adenocarcinoma...
March 11, 2018: Current Research in Translational Medicine
Daniel P Petrylak, Thomas Powles, Joaquim Bellmunt, Fadi Braiteh, Yohann Loriot, Rafael Morales-Barrera, Howard A Burris, Joseph W Kim, Beiying Ding, Constanze Kaiser, Marcella Fassò, Carol O'Hear, Nicholas J Vogelzang
Importance: Atezolizumab (anti-programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective: To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants: Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study...
February 8, 2018: JAMA Oncology
Alberto González-Mohino, Teresa Antequera, Sonia Ventanas, Daniel Caballero, Jorge Mir-Bel, Trinidad Pérez-Palacios
During cooking, there are important changes in meat products depending on the cooked method used as well as on the cooking temperature and time (1-3). The automatic control of these changes would allow the attainment of optimal points of cooking without the subjective criterion of who cooks, which supposes an important improvement in restoration and in domestic area.
February 6, 2018: Journal of the Science of Food and Agriculture
M Ilié, E Szafer-Glusman, V Hofman, E Chamorey, S Lalvée, E Selva, S Leroy, C-H Marquette, M Kowanetz, P Hedge, E Punnoose, P Hofman
Background: Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced NSCLC patients...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
J Adam, N Le Stang, I Rouquette, A Cazes, C Badoual, H Pinot-Roussel, L Tixier, C Danel, F Damiola, D Damotte, F Penault-Llorca, S Lantuéjoul
Background: Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT). Methods: IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
A K Marutha Muthu, P L Cheah, C C Koh, M F Chew, Y F Toh, L M Looi
Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells...
December 2017: Malaysian Journal of Pathology
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Jian-Guo Wei, Kai-Qi Du
We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1a N0 M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein...
December 18, 2017: Thoracic Cancer
Nicolas Piton, Philippe Ruminy, Claire Gravet, Vinciane Marchand, Élodie Colasse, Aude Lamy, Cécile Le Naoures Mear, Fréderic Bibeau, Florent Marguet, Florian Guisier, Mathieu Salaün, Luc Thiberville, Fabrice Jardin, Jean-Christophe Sabourin
Detection of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), and rearranged during transfection (RET) gene rearrangements in lung adenocarcinoma is usually performed by immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH), which is an expensive and difficult technique. Ligation-dependent reverse transcription polymerase chain reaction (RT-PCR) multiplex technique can detect gene rearrangements using probes specifically hybridized to either side of the break point...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Dinesh Pradhan, Milon Amin, Shveta Hooda, Rajiv Dhir, Sheldon Bastacky, Anil V Parwani
BACKGROUND: To study the utility of the laminin immunostain in distinguishing invasive from noninvasive urothelial carcinoma (UC). The distinction is difficult but clinically significant as it can affect the decision to administer intravesical Bacillus Calmette-Guerin or can even lead to cystectomy. MATERIALS AND METHODS: Representative sections of the transurethral resection of bladder tumor specimens from 25 cases of formalin-fixed paraffin-embedded invasive UCs and 25 cases of noninvasive UCs were selected for immunohistochemical (IHC) staining with laminin (Ventana, Oro Valley, AZ, USA)...
October 2017: Journal of Cancer Research and Therapeutics
X L Xu, X Y Tu, R H Shui, Y F Cheng, B H Yu, W T Yang
Objective: To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis. Methods: Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
D Jain, K Jangra, P S Malik, S Arulselvi, K Madan, S Mathur, M C Sharma
OBJECTIVE: Immunohistochemistry (IHC) with anaplastic lymphoma kinase (ALK) antibodies is considered as an economical screening method in lung adenocarcinomas. Automated Ventana D5F3-IHC is approved by US Food and Drug Administration for targeted therapy; however, the automated IHC apparatus are not widely used in most laboratories. We evaluated the performance of ALK IHC using the manual semiquantitative method to assess the concordance with Ventana ALK IHC assay. MATERIALS AND METHODS: We tested 156 cases of primary lung adenocarcinomas for ALK protein expression by D5F3-IHC...
January 2017: Indian Journal of Cancer
P B Wagle, N A Jambhekar, R Kumar, K Prabhash, C S Pramesh, S B Desai, V Noronha, G Karimundackal, A Shah, A Joshi, S G Laskar, S Jiwnani, T Pai, J P Agarwal
INTRODUCTION: Testing for echinoderm microtubule-associated protein-like 4 (EML4) anaplastic lymphoma kinase (ALK) translocation by fluorescence in situ hybridization (FISH) is well established whereas the Food and Drug Administration (FDA) ALK immunohistochemical (IHC) test is relatively new. AIMS AND OBJECTIVE: The aim of this study is to compare FDA-approved ALK IHC test (D5F3 clone) with the standard ALK FISH test. MATERIALS AND METHODS: A validation and a test arm with 100 and 200 cases of Formalin-Fixed, Paraffin-embedded blocks of lung adenocarcinoma, respectively, comprised the material...
January 2017: Indian Journal of Cancer
Shona Hendry, David J Byrne, Gavin M Wright, Richard J Young, Sue Sturrock, Wendy A Cooper, Stephen B Fox
INTRODUCTION: Four different programmed death ligand 1 immunohistochemical assays are approved or in development as companion or complementary diagnostics to different immunotherapeutic agents in lung carcinoma. We sought to determine whether these assays are technically equivalent and whether one antibody can be used on an alternate staining platform. METHODS: Serial sections of tissue microarrays constructed from 368 cases of resected lung cancer were stained for 22C3 and 28-8 on the Dako Link 48 platform (Dako, Carpinteria, Ca) and for SP142 and SP263 on the Ventana Benchmark Ultra platform (Ventana Medical Systems, Tucson, AZ) strictly as per product insert...
March 2018: Journal of Thoracic Oncology
Qiongqiong Gao, Pupu Li, Xiangli Jiang, Zhongli Zhan, Qingna Yan, Bo Zhang, Chun Huang
Introduction: This study determined the prevalence of anaplastic lymphoma kinase (ALK) rearrangement, and identified the associations of ALK rearrangement with clinicopathologic characteristics and treatment outcomes in patients with surgically-resected stage I-III lung adenocarcinoma. Methods: A total of 534 surgically-resected lung adenocarcinoma patients were studied. The prevalence of ALK protein over-expression was determined by a fully-automated immunochemistry assay (with mouse monoclonal Ventana D5F3 antibody), and the associations of ALK rearrangement with clinicopathologic characteristics and treatment outcomes were analyzed...
October 17, 2017: Oncotarget
Katerina Ancevski Hunter, Mark A Socinski, Liza C Villaruz
Immunotherapy with programmed death 1 (PD-1)- and programmed death-ligand 1 (PD-L1)-targeted monoclonal antibodies has dramatically changed the therapeutic and prognostic landscape for several types of malignancy. PD-1 and PD-L1 are immune checkpoint proteins whose binding ultimately result in T cell exhaustion and self-tolerance. Blocking this pathway 'releases the brakes' on the immune system and allows for attack of tumor cells that express PD-L1. The clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents used different immunohistochemical (IHC) platforms with various PD-L1 antibodies to assess for PD-L1 expression on either tumor cells or tumor-infiltrating immune cells...
February 2018: Molecular Diagnosis & Therapy
Bella Hai Nguyen, Renn Montgomery, Mitali Fadia, Jiali Wang, Sayed Ali
AIM: There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome...
November 3, 2017: Asia-Pacific Journal of Clinical Oncology
Maria Hersom, Jan Trøst Jørgensen
Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic co-development model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. When these predictive biomarker assays are linked to a specific drug, they are called companion diagnostics...
October 27, 2017: Therapeutic Drug Monitoring
Reinhard Büttner, John R Gosney, Birgit Guldhammer Skov, Julien Adam, Noriko Motoi, Kenneth J Bloom, Manfred Dietel, John W Longshore, Fernando López-Ríos, Frédérique Penault-Llorca, Giuseppe Viale, Andrew C Wotherspoon, Keith M Kerr, Ming-Sound Tsao
Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and Drug Administration-cleared complementary PD-L1 tests are available for both. PD-L1 IHC assays used to assess PD-L1 expression in patients treated with programmed death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28-8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1 SP263 (SP263)...
December 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Paweł Krawczyk, Bożena Jarosz, Tomasz Kucharczyk, Anna Grenda, Katarzyna Reszka, Juliusz Pankowski, Kamila Wojas-Krawczyk, Marcin Nicoś, Justyna Szumiło, Tomasz Trojanowski, Janusz Milanowski
Different immunohistochemical (IHC) assays were approved for PD-L1 expression examination on tumor cells in qualification to immune-checkpoint inhibitors therapy in NSCLC patients. These assays have some similarities, but also very serious differences. We assessed 2 IHC tests for PD-L1 expression evaluation in NSCLC tumors with different pathological diagnoses and genetic abnormalities. We enrolled 48 NSCLC patients (median age: 65 years) with known status of EGFR and ALK genes. We compared the effectiveness of PD-L1 expression examination of two IHC assays with 22C3 (Dako) and SP142 antibodies (Ventana)...
September 8, 2017: Oncotarget
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