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HER2 amplification

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https://www.readbyqxmd.com/read/28079792/amplification-of-her2-and-top2a-and-deletion-of-top2a-genes-in-a-series-of-taiwanese-breast-cancer
#1
Jim-Ray Chen, Hui-Ping Chien, Kuo-Su Chen, Cheng-Cheng Hwang, Huang-Yang Chen, Kun-Yan Yeh, Tsan-Yu Hsieh, Liang-Che Chang, Yuan-Chun Hsu, Ren-Jie Lu, Chung-Ching Hua
BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28065467/lung-adenocarcinoma-with-muc4-expression-is-associated-with-smoking-status-her2-protein-expression-and-poor-prognosis-clinicopathologic-analysis-of-338-cases
#2
Mariyo Rokutan-Kurata, Akihiko Yoshizawa, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Mizuki Koyama, Shohei Shigeto, Masakazu Fujimoto, Meng Zhang, Satoshi Morita, Hiroshi Date, Hironori Haga
BACKGROUND: MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. PATIENTS AND METHODS: Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28060271/utilizing-functional-genomics-screening-to-identify-potentially-novel-drug-targets-in-cancer-cell-spheroid-cultures
#3
Eamonn Morrison, Patty Wai, Andri Leonidou, Philip Bland, Saira Khalique, Gillian Farnie, Frances Daley, Barrie Peck, Rachael Natrajan
The identification of functional driver events in cancer is central to furthering our understanding of cancer biology and indispensable for the discovery of the next generation of novel drug targets. It is becoming apparent that more complex models of cancer are required to fully appreciate the contributing factors that drive tumorigenesis in vivo and increase the efficacy of novel therapies that make the transition from pre-clinical models to clinical trials. Here we present a methodology for generating uniform and reproducible tumor spheroids that can be subjected to siRNA functional screening...
December 26, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28052014/met-overexpression-gene-amplification-and-relevant-clinicopathological-features-in-gastric-adenocarcinoma
#4
Jing Zhang, Lei Guo, Xiuyun Liu, Wenbin Li, Jianming Ying
This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#5
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28043647/the-morphological-spectrum-of-salivary-gland-type-tumours-of-the-breast
#6
REVIEW
Maria P Foschini, Luca Morandi, Sofia Asioli, Gianluca Giove, Angelo G Corradini, Vincenzo Eusebi
Salivary gland like tumours of the breast constitute a wide spectrum of entities each one showing peculiar features and clinical behaviour. They can be subdivided as follows: (1) tumours showing pure myoepithelial cell differentiation, such as pure benign and malignant myoepitheliomas; (2) tumours with mixed epithelial and myoepithelial cell differentiation, such as pleomorphic adenoma, adenomyoepithelioma and adenoid cystic carcinoma; and (3) tumours with pure epithelial cell differentiation, such as acinic cell carcinoma, oncocytic carcinoma, mucoepidermoid carcinoma and polymorphous adenocarcinoma...
December 30, 2016: Pathology
https://www.readbyqxmd.com/read/28042991/external-validation-of-a-published-nomogram-for-prediction-of-brain-metastasis-in-patients-with-extra-cerebral-metastatic-breast-cancer-and-risk-regression-analysis
#7
Ludivine Genre, Henri Roché, Léonel Varela, Dorra Kanoun, Monia Ouali, Thomas Filleron, Florence Dalenc
BACKGROUND: Survival of patients with metastatic breast cancer (MBC) suffering from brain metastasis (BM) is limited and this event is usually fatal. In 2010, the Graesslin's nomogram was published in order to predict subsequent BM in patients with breast cancer (BC) with extra-cerebral metastatic disease. This model aims to select a patient population at high risk for BM and thus will facilitate the design of prevention strategies and/or the impact of early treatment of BM in prospective clinical studies...
December 30, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/28040715/prolonged-response-to-her2-directed-therapy-in-a-patient-with-her2-amplified-rapidly-progressive-metastatic-colorectal-cancer
#8
Aparna Parikh, Chloe Atreya, W Michael Korn, Alan P Venook
HER2 gene amplifications and activating mutations in the HER2 receptor tyrosine kinase are present in 4% of metastatic colorectal cancers (mCRCs). HER2-targeted therapy is not standard of care, although preclinical and clinical data suggest that patients with HER2 amplifications and/or HER2-activating mutations may benefit from HER2-directed therapy. HER2 amplifications and activating mutations have also been implicated in resistance to anti-epidermal growth factor receptor-based therapy. This report describes a patient with KRAS, NRAS, and BRAF wild-type mCRC who experienced disease progression on first-line treatment with FOLFIRI and cetuximab after only 5 months, and subsequently experienced progression on second-line treatment with capecitabine and oxaliplatin plus bevacizumab after 2 months with significant functional decline...
January 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28039535/use-of-droplet-digital-pcr-for-quantitative-and-automatic-analysis-of-the-her2-status-in-breast-cancer-patients
#9
Kazutaka Otsuji, Takeshi Sasaki, Atsushi Tanaka, Akiko Kunita, Masako Ikemura, Keisuke Matsusaka, Keiichiro Tada, Masashi Fukayama, Yasuyuki Seto
PURPOSE: Digital polymerase chain reaction (dPCR) has been used to yield an absolute measure of nucleic acid concentrations. Recently, a new method referred to as droplet digital PCR (ddPCR) has gained attention as a more precise and less subjective assay to quantify DNA amplification. We demonstrated the usefulness of ddPCR to determine HER2 gene amplification of breast cancer. METHODS: In this study, we used ddPCR to measure the HER2 gene copy number in clinical formalin-fixed paraffin-embedded samples of 41 primary breast cancer patients...
December 30, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28039357/key-survival-factor-mcl-1-correlates-with-sensitivity-to-combined-bcl-2-bcl-xl-blockade
#10
Michelle Williams, Linus Lee, Donna J Hicks, Meghan M Joly, David Elion, Bushra Rahman, Courtney McKernan, Violeta Sanchez, Justin M Balko, Thomas Stricker, Monica Valeria Estrada, Rebecca S Cook
: An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use anti-apoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of anti-apoptotic Bcl-2 family members in clinical breast cancer datasets, revealed greater expression and more frequent gene amplification of MCL1 as compared to BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28034454/comprehensive-genomic-sequencing-and-the-molecular-profiles-of-clinically-advanced-breast-cancer
#11
Jeffrey S Ross, Laurie M Gay
Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events...
December 26, 2016: Pathology
https://www.readbyqxmd.com/read/28032917/well-differentiated-invasive-breast-cancers-with-equivocal-her2-immunohistochemistry-what-is-the-yield-of-routine-reflex-in-situ-hybridization-testing
#12
Gillian Charlotte Bethune, Alexandra Sophie Louise Pettit, Daniel Veldhuijzen van Zanten, Penelope Jane Barnes
AIMS: The 2013 ASCO/CAP HER2 guidelines recommend testing all invasive breast cancers for HER2, typically with IHC followed by ISH when IHC is equivocal. As well-differentiated breast cancers are rarely HER2 positive, we assessed the value of routine reflex HER2 ISH testing for this subset of breast cancers. METHODS AND RESULTS: We collected HER2 IHC 2+ cases and FISH data from primary breast cancers with well-differentiated tumor types (grade 1 ductal carcinomas, classic lobular carcinomas, tubular, cribriform and pure mucinous carcinomas) at our centre from 2010-2015...
December 29, 2016: Histopathology
https://www.readbyqxmd.com/read/28028387/her2-neu-protein-expression-and-oncogene-amplification-in-gastric-carcinoma-with-clinico-pathological-correlation-in-egyptian-patients
#13
Ahmed Abdel Hadi, Ali El Hindawi, Amal Hareedy, Heba Khalil, Ranya Al Ashiry, Shady Elia, Ahmed Sadek, Mona Magdy, Rafatt Atta, Amgad Anas, Hisham Bakr, Olfat Hammam
AIM: Amplification of the Her2/neu gene and overexpression of the Her2/neu protein in gastric carcinoma (GC) is a golden criterion for target therapy with trastuzumab (Herceptin). We aim to evaluate the immunohistochemical protein expression and amplification of the oncogene Her2/neu by FISH technique in the epithelial gastric carcinoma and to compare their association with different clinicopathologic parameters aiming at identifying positive cases that may benefit from targeted therapy...
December 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28027945/next-generation-assessment-of-erbb2-human%C3%A2-epidermal-growth-factor-receptor-2-amplification-status-clinical-validation-in-the-context-of-a-hybrid-capture-based-comprehensive-solid-tumor-genomic-profiling-assay
#14
Dara S Ross, Ahmet Zehir, Donavan T Cheng, Ryma Benayed, Khedoudja Nafa, Jaclyn F Hechtman, Yelena Y Janjigian, Britta Weigelt, Pedram Razavi, David M Hyman, José Baselga, Michael F Berger, Marc Ladanyi, Maria E Arcila
Establishing ERBB2 [human epidermal growth factor receptor 2 (HER2)] amplification status in breast and gastric carcinomas is essential to patients' treatment plans. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) constitute the current standard for assessment. With further advancements in genomic medicine, new clinically relevant biomarkers are rapidly emerging and options for targeted therapy are increasing in patients with advanced disease, driving the need for comprehensive molecular profiling...
December 24, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28027327/mutational-profile-of-metastatic-breast-cancers-a-retrospective-analysis
#15
Celine Lefebvre, Thomas Bachelot, Thomas Filleron, Marion Pedrero, Mario Campone, Jean-Charles Soria, Christophe Massard, Christelle Lévy, Monica Arnedos, Magali Lacroix-Triki, Julie Garrabey, Yannick Boursin, Marc Deloger, Yu Fu, Frédéric Commo, Véronique Scott, Ludovic Lacroix, Maria Vittoria Dieci, Maud Kamal, Véronique Diéras, Anthony Gonçalves, Jean-Marc Ferrerro, Gilles Romieu, Laurence Vanlemmens, Marie-Ange Mouret Reynier, Jean-Christophe Théry, Fanny Le Du, Séverine Guiu, Florence Dalenc, Gilles Clapisson, Hervé Bonnefoi, Marta Jimenez, Christophe Le Tourneau, Fabrice André
BACKGROUND: Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. METHODS AND FINDINGS: Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28008968/interaction-of-cytokeratin-19-head-domain-and-her2-in-the-cytoplasm-leads-to-activation-of-her2-erk-pathway
#16
Tomoaki Ohtsuka, Masakiyo Sakaguchi, Hiromasa Yamamoto, Shuta Tomida, Katsuyoshi Takata, Kazuhiko Shien, Shinsuke Hashida, Tomoko Miyata-Takata, Mototsugu Watanabe, Ken Suzawa, Junichi Soh, Chen Youyi, Hiroki Sato, Kei Namba, Hidejiro Torigoe, Kazunori Tsukuda, Tadashi Yoshino, Shinichiro Miyoshi, Shinichi Toyooka
HER2 is a receptor tyrosine kinase and its upregulation via activating mutations or amplification has been identified in some malignant tumors, including lung cancers. Because HER2 can be a therapeutic target in HER2-driven malignancies, it is important to understand the molecular mechanisms of HER2 activation. In the current study, we identified that cytokeratin 19 (KRT19) binds to HER2 at the inside face of plasma membrane. HER2 and KRT19, which were concurrently introduced to a human embryonic kidney 293 T cells, revealed an association with each other and resulted in phosphorylation of HER2 with the subsequent activation of a downstream Erk-associated pathway...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28006087/significant-and-durable-clinical-benefit-from-trastuzumab-in-2-patients-with-her2-amplified-salivary-gland-cancer-and-a-review-of-the-literature
#17
Lauren M Thorpe, Alexa B Schrock, Rachel L Erlich, Vincent A Miller, James Knost, Nguyet Le-Lindqwister, Srinivas Jujjavarapu, Siraj M Ali, Jane J Liu
BACKGROUND: Salivary ductal carcinoma and carcinoma ex pleomorphic adenoma (CEPA) are aggressive salivary gland cancers with poor prognosis. The standard of care is resection with or without radiotherapy, and there are no established systemic therapy options. METHODS: We describe 1 patient with metastatic CEPA and 1 patient with metastatic recurrent salivary duct carcinoma whose tumors were evaluated by comprehensive genomic profiling. Testing identified human epidermal growth factor receptor 2 (HER2) amplification in both patients, and an additional activating HER2 mutation in the CEPA case...
December 22, 2016: Head & Neck
https://www.readbyqxmd.com/read/27993117/role-of-genomic-alterations-in-her2-positive-breast-carcinoma-focus-on-susceptibility-and-trastuzumab-therapy
#18
Heena Singla, Sourav Kalra, Preeti Kheterpal, Vinod Kumar, Anjana Munshi
Breast cancer is the most frequently diagnosed life-threatening malignancy among women, across the globe. HER2 positive is a distinct breast cancer subtype, on account of its unique biology and physiological behavior. Amplification of HER2 oncogene/polysomy 17 leads to HER2 overexpression that is a significant causal implication in HER2 positive breast cancer. HER2 gene variants, as well as other genes/gene variants, are involved in its overexpression, disease prognosis and in predicting the susceptibility towards HER2 positive breast cancer Trastuzumab (Herceptin) is the most commonly used therapy for treating patients with HER2 positive status...
December 15, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27993109/recent-insights-into-the-development-of-preclinical-trastuzumab-resistant-her2-breast-cancer-models
#19
Paula González-Alonso, Ion Cristóbal, Sandra Zazo, Ester Martín-Aparicio, Cristina Chamizo, Juan Madoz-Gúrpide, Ana Rovira, Pilar Eroles, Ana Lluch, Joan Albanell, Federico Rojo
BACKGROUND: Overexpression and amplification of the human epidermal growth factor receptor 2 (HER2) occurs in 20% of total breast carcinomas. HER2-overexpression is implicated in disease initiation and progression and associated with poor prognosis. Trastuzumab, a humanized monoclonal antibody, is the standard HER2-targeted therapy for early and metastatic HER2-amplified breast cancer patients. Trastuzumab has significantly increased clinical benefit in HER2+ metastatic and adjuvant settings, however, it is not effective for many patients due to primary or acquired resistance to the drug...
December 16, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27981460/her2-her3-pathway-in-biliary-tract-malignancies-systematic-review-and-meta-analysis-a-potential-therapeutic-target
#20
Salvatore Galdy, Angela Lamarca, Mairéad G McNamara, Richard A Hubner, Chiara A Cella, Nicola Fazio, Juan W Valle
Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric cancer, whereas human epidermal growth factor receptor 3 (HER3) is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 overexpression and amplification in biliary tract cancers (BTCs). An electronic search of MEDLINE, American Society of Clinical Oncology (ASCO), European Society of Medical Oncology Congress (ESMO), and American Association for Cancer Research (AACR) was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridization (ISH) in BTCs...
December 15, 2016: Cancer Metastasis Reviews
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