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HER2 amplification

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https://www.readbyqxmd.com/read/29156800/comparative-molecular-analyses-of-left-sided-colon-right-sided-colon-and-rectal-cancers
#1
Mohamed E Salem, Benjamin A Weinberg, Joanne Xiu, Wafik S El-Deiry, Jimmy J Hwang, Zoran Gatalica, Philip A Philip, Anthony F Shields, Heinz-Josef Lenz, John L Marshall
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151938/comparison-of-her2-and-lauren-classification-between-biopsy-and-surgical-resection-samples-primary-and-metastatic-samples-of-gastric-cancer
#2
Miao-Zhen Qiu, Si-Mei Shi, Min Chen, Jing Wang, Qi-Nian Wu, Hui Sheng, Hui-Zhong Zhang, Jing-Ping Yun, Zhi-Wei Zhou, Feng-Hua Wang, Da-Jun Yang, Rui-Hua Xu
Purpose: Patients with advanced or metastatic adenocarcinoma of the stomach or esophagogastric junction for whom trastuzumab therapy is being considered, assessment for tumor human epidermal growth factor receptor-2 (HER2) status is necessary. Can the HER2 status and Lauren classification of the biopsy sample truly represent the HER2 status in the gastric cancer? Methods: Formalin-fixed, paraffin-embedded sections of 116 pair surgically resected and biopsy specimens as well as 80 pair primary and metastatic lesions of gastric cancer patients were analyzed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29146056/comparison-of-her2-status-determination-methods-in-her2-2-patients-manual-fluorescent-in-situ-hybridization-fish-vs-dual-silver-enhanced-in-situ-hybridization-sish
#3
Burcin Pehlivanoglu, Gurdeniz Serin, Levent Yeniay, Osman Zekioglu, Erhan Gokmen, Necmettin Ozdemir
HER2 amplification has been demonstrated in 15-25% of invasive breast carcinomas and can be assessed using immunohistochemical and in situ hybridization methods. Here, we compared the accuracy of dual SISH to manual FISH in HER2 (2+) breast carcinoma and evaluated the feasibility of dual SISH method in routine practice. Sixty HER2 (2+) consecutive tumor samples diagnosed between January 2009 and February 2013 were selected. Demographic, histological and immunohistochemical features and FISH results were recruited from patient records and compared to dual SISH results...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29140993/prognostic-significance-of-cyclin-d1-protein-expression-and-gene-amplification-in-invasive-breast-carcinoma
#4
Angela B Ortiz, Diego Garcia, Yolanda Vicente, Magda Palka, Carmen Bellas, Paloma Martin
The oncogenic capacity of cyclin D1 has long been established in breast cancer. CCND1 amplification has been identified in a subset of patients with poor prognosis, but there are conflicting data regarding the predictive value of cyclin D1 protein overexpression. This study was designed to analyze the expression of cyclin D1 and its correlation with CCND1 amplification and their prognostic implications in invasive breast cancer. By using the tissue microarray technique, we performed an immunohistochemical study of ER, PR, HER2, p53, cyclin D1, Ki67 and p16 in 179 invasive breast carcinoma cases...
2017: PloS One
https://www.readbyqxmd.com/read/29137369/lrh-1-expression-patterns-in-breast-cancer-tissues-are-associated-with-tumour-aggressiveness
#5
Jia-Min B Pang, Ramyar Molania, Ashwini Chand, Kevin Knower, Elena A Takano, David J Byrne, Thomas Mikeska, Ewan K A Millar, Cheok Soon Lee, Sandra A O'Toole, Colin Clyne, Kylie L Gorringe, Alexander Dobrovic, Stephen B Fox
The significance and regulation of liver receptor homologue 1 (LRH-1, NR5A2), a tumour-promoting transcription factor in breast cancer cell lines, is unknown in clinical breast cancers. This study aims to determine LRH-1/NR5A2 expression in breast cancers and relationship with DNA methylation and tumour characteristics. In The Cancer Genome Atlas breast cancer cohort NR5A2 expression was positively associated with intragenic CpG island methylation (1.4-fold expression for fully methylated versus not fully methylated, p=0...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135104/clinicopathological-and-prognostic-significance-of-cyclin-d1-amplification-in-patients-with-breast-cancer-a-meta-analysis
#6
Qi He, Jingxun Wu, Xin-Li Liu, Yi-Han Ma, Xiao-Ting Wu, Wen-Yi Wang, Han-Xiang An
PURPOSE: Cyclin D1 plays a critical role in tumorigenesis and the regulation of the G1/S transition in the cell cycle. The relationship between cyclin D1 amplification and clinicopathological parameters in patients with breast cancer remains controversial and its impact on survival outcome is not completely clear. We conducted a meta-analysis to investigate the associations between cyclin D1 gene amplification and certain clinicopathological characteristics and the prognosis in breast cancer...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29131161/rapid-virtual-hematoxylin-and-eosin-histology-of-breast-tissue-specimens-using-a-compact-fluorescence-nonlinear-microscope
#7
Lucas C Cahill, Michael G Giacomelli, Tadayuki Yoshitake, Hilde Vardeh, Beverly E Faulkner-Jones, James L Connolly, Chi-Kuang Sun, James G Fujimoto
Up to 40% of patients undergoing breast conserving surgery for breast cancer require repeat surgeries due to close to or positive margins. The lengthy processing required for evaluating surgical margins by standard paraffin-embedded histology precludes its use during surgery and therefore, technologies for rapid evaluation of surgical pathology could improve the treatment of breast cancer by reducing the number of surgeries required. We demonstrate real-time histological evaluation of breast cancer surgical specimens by staining specimens with acridine orange (AO) and sulforhodamine 101 (SR101) analogously to hematoxylin and eosin (H&E) and then imaging the specimens with fluorescence nonlinear microscopy (NLM) using a compact femtosecond fiber laser...
November 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29127587/copanlisib-first-global-approval
#8
Anthony Markham
Bayer are developing copanlisib (Aliqopa™)-a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor-as a treatment for various haematological and solid malignancies. The US FDA has granted copanlisib accelerated approval for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic therapies based on the results of a phase II trial. Phase III trials are underway evaluating copanlisib as treatment for relapsed/refractory diffuse large B-cell lymphoma and in combination with rituximab or rituximab-based chemotherapy or standard immunochemotherapy in patients with relapsed indolent B-cell non-Hodgkin's lymphoma...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29125480/methods-and-significance-of-the-combined-detection-of-her2-gene-amplification-and-chemosensitivity-in-gastric-cancer
#9
Yang-Kun Wang, Bin-Feng Yang, Tian Yun, Chao-Ya Zhu, Cong-Yang Li, Bo Jiang, Gong-Ping Wang, Su-Nan Wang, Ying-Ying Li, Mei-Ling Zhu
OBJECTIVE: This study aims to investigate the significance of combined detection of HER2 gene amplification and chemosensitivity in gastric cancer. METHODS: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and fluorescence reverse-transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of HER2 protein, HER2 gene amplification and the mRNA expression of ERCC1, TUBB3 and TYMS genes in 135 cases of gastric carcinoma...
November 3, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29122777/genetic-predictors-of-response-to-systemic-therapy-in-esophagogastric-cancer
#10
Yelena Y Janjigian, Francisco Sanchez-Vega, Philip Jonsson, Walid K Chatila, Jaclyn F Hechtman, Geoffrey Y Ku, Jamie C Riches, Yaelle Tuvy, Ritika Kundra, Nancy Bouvier, Efsevia Vakiani, Jianjiong Gao, Zachary J Heins, Benjamin E Gross, David P Kelsen, Liying Zhang, Vivian E Strong, Mark Schattner, Hans Gerdes, Daniel G Coit, Manjit Bains, Zsofia K Stadler, Valerie W Rusch, David R Jones, Daniela Molena, Jinru Shia, Mark E Robson, Marinela Capanu, Sumit Middha, Ahmet Zehir, David M Hyman, Maurizio Scaltriti, Marc Ladanyi, Neal Rosen, David H Ilson, Michael F Berger, Laura Tang, Barry S Taylor, David B Solit, Nikolaus Schultz
The incidence of esophagogastric cancer is rapidly rising but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of metastatic esophagogastric cancer patients. There was no association between HRD defects and response to platinum-based chemotherapy. Patients with MSI-H tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy...
November 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29113162/retrospective-analysis-of-the-association-between-human-epidermal-growth-factor-receptor-2-amplification-and-chromosome-enumeration-probe-17-status-in-patients-with-breast-cancer
#11
Xiaoyu Hu, Yanan Li, Dong Yuan, Ruohan Li, Lingquan Kong, Hongyuan Li, Zhu Yang, Qiubo Yu
The aim of the present study was to identify potential human epidermal growth factor receptor 2 (HER2) amplification, according to American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) 2013 HER2 testing guidelines, in patients previously determined not to possess HER2 amplification, in accordance with previous 2007 guidelines. Potential discrepancies may arise from chromosome enumeration probe 17 (CEP17) amplification, deletion, polysomyor monosomy. HER2, CEP17, tumor protein p53 (TP53) and retinoic acid receptor α (RARA) genes from 67 patient specimens with suspected amplification, polysomy or monosomy of CEP17 were analyzed using fluorescence in situ hybridization...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29110627/the-impact-of-translational-research-in-breast-cancer-care-can-we-improve-the-therapeutic-scenario
#12
Francesco Perri, Giuseppe Buono, Francesco Schettini, Grazia Arpino, Roberto Bianco, Carmen Criscitiello, Sabino De Placido, Mario Giuliano
Traditionally, breast cancer (BC) is divided into different immunohistochemically (IHC)-defined subtypes, according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches...
November 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29100393/down-regulation-of-traditional-oncomirs-in-plasma-of-breast-cancer-patients
#13
Dana Jurkovicova, Bozena Smolkova, Monika Magyerkova, Zuzana Sestakova, Viera Horvathova Kajabova, Ludovit Kulcsar, Iveta Zmetakova, Lenka Kalinkova, Tomas Krivulcik, Marian Karaba, Juraj Benca, Tatiana Sedlackova, Gabriel Minarik, Zuzana Cierna, Ludovit Danihel, Michal Mego, Miroslav Chovanec, Ivana Fridrichova
Deregulated expression of microRNAs has the oncogenic or tumor suppressor function in cancer. Since miRNAs in plasma are highly stable, their quantification could contribute to more precise cancer diagnosis, prognosis and therapy prediction. We have quantified expression of seven oncomiRs, namely miR-17/92 cluster (miR-17, miR-18a, miR-19a and miR-20a), miR-21, miR-27a and miR-155, in plasma of 137 breast cancer (BC) patients. We detected down-regulation of six miRNAs in patients with invasive BC compared to controls; however, only miR-20a and miR-27a down-regulations were statistically significant...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100278/somatic-mutations-in-salivary-duct-carcinoma-and-potential-therapeutic-targets
#14
Timothy K Khoo, Bing Yu, Joel A Smith, Angus J Clarke, Peter P Luk, Christina I Selinger, Kate L Mahon, Spiridoula Kraitsek, Carsten Palme, Michael J Boyer, Marcel E Dinger, Mark J Cowley, Sandra A O'Toole, Jonathan R Clark, Ruta Gupta
Background: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29076877/the-role-of-molecular-testing-in-the-differential-diagnosis-of-salivary-gland-carcinomas
#15
Alena Skálová, Göran Stenman, Roderick H W Simpson, Henrik Hellquist, David Slouka, Tomas Svoboda, Justin A Bishop, Jennifer L Hunt, Ken-Ichi Nibu, Alessandra Rinaldo, Vincent Vander Poorten, Kenneth O Devaney, Petr Steiner, Alfio Ferlito
Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion...
October 26, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29069787/proteasome-inhibitors-prevent-bi-directional-her2-estrogen-receptor-cross-talk-leading-to-cell-death-in-endocrine-and-lapatinib-resistant-her2-er-breast-cancer-cells
#16
Sonja Thaler, Marcus Schmidt, Sven Roβwag, Gitta Thiede, Arno Schad, Jonathan P Sleeman
Amplification and/or overexpression of the human epidermal growth factor 2 (HER2) oncogene occurs in about 13-15% of invasive breast cancer and triggers breast cancer cell proliferation, survival and metastatic progression. Around half of all breast cancers with HER2 overexpression co-express hormone receptors (HR) such as those for estrogen and progesterone. Aberrant signaling through HER2 and other members of the HER-family mediates endocrine-resistance in estrogen receptor alpha (ERα) positive breast cancer...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29067216/genotyping-tumour-dna-in-cerebrospinal-fluid-and-plasma-of-a-her2-positive-breast-cancer-patient-with-brain-metastases
#17
Giulia Siravegna, Elena Geuna, Benedetta Mussolin, Giovanni Crisafulli, Alice Bartolini, Danilo Galizia, Laura Casorzo, Ivana Sarotto, Maurizio Scaltriti, Anna Sapino, Alberto Bardelli, Filippo Montemurro
BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment...
2017: ESMO Open
https://www.readbyqxmd.com/read/29053266/structure-activity-relationships-of-new-natural-product-based-diaryloxazoles-with-selective-activity-against-androgen-receptor-positive-breast-cancer-cells
#18
Andrew J Robles, Shelby McCowen, Shengxin Cai, Michaels Glassman, Francisco Ruiz, Robert H Cichewicz, Stanton F McHardy, Susan L Mooberry
Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC...
November 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29046940/gastric-cancer-immunohistochemical-classification-of-molecular-subtypes-and-their-association-with-clinicopathological-characteristics
#19
Eva-Maria Birkman, Naziha Mansuri, Samu Kurki, Annika Ålgars, Minnamaija Lintunen, Raija Ristamäki, Jari Sundström, Olli Carpén
Gastric cancer is traditionally divided into intestinal and diffuse histological subtypes, but recent molecular analyses have led to novel classification proposals based on genomic alterations. While the intestinal- and diffuse-type tumours are distinguishable from each other at the molecular level, intestinal-type tumours have more diverse molecular profile. The technology required for comprehensive molecular analysis is expensive and not applicable for routine clinical diagnostics. In this study, we have used immunohistochemistry and in situ hybridisation in molecular classification of gastric adenocarcinomas with an emphasis on the intestinal subtype...
October 19, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29045518/negative-hyper-selection-of-metastatic-colorectal-cancer-patients-for-anti-egfr-monoclonal-antibodies-the-pressing-case-control-study
#20
C Cremolini, F Morano, R Moretto, R Berenato, E Tamborini, F Perrone, D Rossini, A Gloghini, A Busico, G Zucchelli, C Baratelli, E Tamburini, M Tampellini, E Sensi, G Fucà, C Volpi, M Milione, M Di Maio, G Fontanini, F De Braud, A Falcone, F Pietrantonio
Background: Refining the selection of metastatic colorectal cancer (mCRC) patients candidates for anti-EGFR monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signaling pathways, have been suggested by preclinical and retrospective studies. Patients and methods: We conducted this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations (PRESSING panel), including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions, and HER2/PI3K/PTEN/AKT1 mutations...
September 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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