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HER2 amplification

Jung-Soo Pyo, Guhyun Kang, Hyunjin Cho
PURPOSE: The aim of the present study was to elucidate the clinicopathological significance and diagnostic accuracy of immunohistochemistry (IHC) for determining the mesenchymal epidermal transition (c-MET) expression in patients with gastric cancer (GC). MATERIALS AND METHODS: The present meta-analysis investigated the correlation between c-MET expression as determined by IHC and the clinicopathological parameters in 8,395 GC patients from 37 studies that satisfied the eligibility criteria...
September 2016: Journal of Gastric Cancer
Shailaja Shukla, Bhawana Komal Singh, Om Prakash Pathania, Manjula Jain
BACKGROUND & OBJECTIVES: The proto-oncogene HER2/neu has been extensively studied in breast cancer patients. Serum levels of HER2/neu by ELISA in breast cancer patients were compared with tissue HER2/neu expression and with other clinicopathological parameters with the aim to investigate whether the serum assay could replace the established tests (IHC/FISH) for HER-2 status. METHODS: Blood and Tru-cut biopsy samples were collected for determining HER2/neu status in 64 breast cancer patients...
May 2016: Indian Journal of Medical Research
Jacob A Miller, Elizabeth E Bennett, Roy Xiao, Rupesh Kotecha, Samuel T Chao, Michael A Vogelbaum, Gene H Barnett, Lilyana Angelov, Erin S Murphy, Jennifer S Yu, Manmeet S Ahluwalia, John H Suh, Alireza M Mohammadi
BACKGROUND: The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN...
September 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Morgan Ballard, Florencia Jalikis, Gregor Krings, Rodney A Schmidt, Yunn-Yi Chen, Mara H Rendi, Suzanne M Dintzis, Kristin C Jensen, Robert B West, Richard K Sibley, Megan L Troxell, Kimberly H Allison
The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Tosol Yu, Bong Jun Cho, Eun Jung Choi, Ji Min Park, Dan Hyo Kim, In Ah Kim
Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification...
October 12, 2016: Oncotarget
Matthias Christgen, Jana L van Luttikhuizen, Mieke Raap, Peter Braubach, Lars Schmidt, Danny Jonigk, Friedrich Feuerhake, Ulrich Lehmann, Brigitte Schlegelberger, Hans H Kreipe, Doris Steinemann
HER2/ERBB2 amplification/overexpression determines the eligibility of breast cancer patients to HER2-targeted therapy. This study evaluates the agreement between ERBB2 copy number assessment by fluorescence in situ hybridization, a standard method recommended by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP), and newly available DNA extraction-based methods. A series of n=29 formalin-fixed paraffin-embedded breast cancers were subjected to ERBB2 copy number assessment by fluorescence in situ hybridization (FISH, Vysis, Abbott)...
October 3, 2016: Oncotarget
Koji Arihiro, Miyo Oda, Katsunari Ogawa, Yoshie Kaneko, Tomomi Shimizu, Yuna Tanaka, Yukari Marubashi, Katsunari Ishida, Chikako Takai, Chie Taoka, Shuji Kimura, Noriyuki Shiroma
OBJECTIVES: Although updated HER2 testing guidelines have been improved by a collaboration between the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) in 2013, HER2 evaluation is still problematic because of issues involving CEP17 polysomy, heterogeneity, and HER2 score 2+ cases. The aim of this retrospective study was to evaluate the relationship between HER2 gene heterogeneity, or so called CEP17 polysomy, using breast carcinoma cells sampled by scraping and the IHC score graded by automated image analysis using whole slide image...
October 3, 2016: Pathology, Research and Practice
Muhammad Afzal, Mohammed Amir, Muhammad Jawad Hassan, Muhammad Sikander Hussain, Muhammad Naveed Aziz, Sheeba Murad, Iram Murtaza, Mariam Anees, Aneesa Sultan
No abstract text is available yet for this article.
September 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Debora Fumagalli, David Venet, Michail Ignatiadis, Hatem A Azim, Marion Maetens, Françoise Rothé, Roberto Salgado, Ian Bradbury, Lajos Pusztai, Nadia Harbeck, Henry Gomez, Tsai-Wang Chang, Maria Antonia Coccia-Portugal, Serena Di Cosimo, Evandro de Azambuja, Lorena de la Peña, Paolo Nuciforo, Jan C Brase, Jens Huober, José Baselga, Martine Piccart, Sherene Loi, Christos Sotiriou
Importance: In neoadjuvant trials, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancers with dual HER2 blockade resulted in increased pathologic complete response (pCR) rates compared with each targeted agent alone. Amplification and/or overexpression of HER2 currently remains the only biomarker for therapeutic decisions, but it is insufficient to explain the heterogeneous response to anti-HER2 agents. Objective: To investigate the ability of clinically and biologically relevant genes and gene signatures (GSs) measured by RNA sequencing to predict the efficacy of anti-HER2 agents...
September 29, 2016: JAMA Oncology
Apurva Jain, Lawrence N Kwong, Milind Javle
Biliary tract cancers are relatively uncommon, have an aggressive disease course and a dismal clinical outcome. Until recently, there have been very few clinical advances in the management of these patients and gemcitabine-based chemotherapy has been the only widely accepted systemic therapy. The advent of next generation sequencing technologies can potentially change the treatment paradigm of this disease. Targeted therapy directed against actionable mutations and identification of molecular subsets with distinct prognostic significance is now feasible in clinical practice...
November 2016: Current Treatment Options in Oncology
Chiara Cremolini, Filippo Pietrantonio
In metastatic colorectal cancer, the optimization of upfront treatment and the continuum of care based on patients' exposure to multiple treatment lines have reached a plateau of efficacy. Therefore, a paradigm shift is ongoing towards precision medicine and personalized treatments based on the specific molecular features of the disease. In this perspective, the improved knowledge of disease biology coming from the lab has prompted a rapid translation from bench to bedside of newer targeted strategies. Here, we focus on the most promising biomarkers already included or close to adoption in daily clinical practice...
September 20, 2016: Tumori
Sahar Aly Daoud, Wesam Maghawri Ismail, Mohamed Salah Abdelhamid, Tamer Mohamed Nabil, Sahar Aly Daoud
HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well defined either...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Nnennaya Kanu, Maria Antonietta Cerone, Gerald Goh, Lykourgos-Panagiotis Zalmas, Jirina Bartkova, Michelle Dietzen, Nicholas McGranahan, Rebecca Rogers, Emily K Law, Irina Gromova, Maik Kschischo, Michael I Walton, Olivia W Rossanese, Jiri Bartek, Reuben S Harris, Subramanian Venkatesan, Charles Swanton
BACKGROUND: The APOBEC3 family of cytidine deaminases mutate the cancer genome in a range of cancer types. Although many studies have documented the downstream effects of APOBEC3 activity through next-generation sequencing, less is known about their upstream regulation. In this study, we sought to identify a molecular basis for APOBEC3 expression and activation. RESULTS: HER2 amplification and PTEN loss promote DNA replication stress and APOBEC3B activity in vitro and correlate with APOBEC3 mutagenesis in vivo...
2016: Genome Biology
Diogo Morbeck, Aline Caldart Tregnago, Glauco Baiocchi Netto, Carlos Sacomani, Patricia Maria Peresi, Cynthia Toledo Osório, Luciana Schutz, Stephania Martins Bezerra, Louise de Brot, Isabela Werneck Cunha
AIMS: GATA3 has been reported as a specific urothelial marker among organs in the pelvic region and has been classified as highly sensitive and specific for urothelial and breast carcinomas. Our aim was to verify GATA3 expression in extramammary Paget disease (EMPD) and check if it can be use to differentiate primary vulvar Paget disease (PVPD) from pagetoid urothelial intraepithelial neoplasia (PUIN). Also we analyzed Her2 protein expression and HER2 gene amplification and its role as prognostic factors in EMPD METHODS AND RESULTS: We analyzed GATA3 and Her2 expression in 11 primary vulvar Paget disease and also 2 PUIN cases...
September 16, 2016: Histopathology
Daniela Furrer, Simon Jacob, Chantal Caron, François Sanschagrin, Louise Provencher, Caroline Diorio
AIM: We examined an economical method for evaluating the amplification of the human epidermal growth factor receptor 2 (HER2) gene in breast cancer specimens. MATERIALS AND METHODS: We compared HER2 amplification determined by fluorescence in situ hybridization (FISH) on whole-tissue (WT) blocks used for diagnostic and on tissue microarray (TMA) sections for a cohort of 521 consecutive patients with breast cancer. In a subset of 116 patients, we examined HER2 concordance from the WT section and a TMA section from a randomly chosen additional block (a proxy of the core biopsy)...
September 2016: Anticancer Research
Katherine B Geiersbach, Carlynn Willmore-Payne, Alexandra V Pasi, Christian N Paxton, Theresa L Werner, Xinjie Xu, Carl T Wittwer, H Evin Gulbahce, Erinn Downs-Kelly
OBJECTIVES: Guidelines for HER2 testing define an equivocal range for HER2 using two approved testing methods, immunohistochemistry (IHC) and in situ hybridization (ISH). We investigated genome-wide copy number alterations in this subgroup. METHODS: Ten breast cancers with equivocal HER2 status by both IHC and ISH were analyzed by single-nucleotide polymorphism cytogenomic microarray (SNP array). DNA ploidy analysis by flow cytometry was performed on nine cases with sufficient material remaining...
October 2016: American Journal of Clinical Pathology
Yulong Li, Rui Zhang, Yanxi Han, Tian Lu, Jiansheng Ding, Kuo Zhang, Guigao Lin, Jiehong Xie, Jinming Li
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is as a target gene for trastuzumab in patients with breast cancer. Accurate determination of HER2 status and strict quality control are necessary to ensure reproducibility and accuracy of the techniques used for the determination of HER2 status. METHODS: We used three different types of samples: formalin-fixed and paraffin-embedded (FFPE) samples prepared from cell lines, agarose gel samples using cell lines, and xenograft tumor samples...
2016: Diagnostic Pathology
Fei Ma, Wenjie Zhu, Yanfang Guan, Ling Yang, Xuefeng Xia, Shanshan Chen, Qiao Li, Xiuwen Guan, Zongbi Yi, Haili Qian, Xin Yi, Binghe Xu
BACKGROUND: Most studies utilizing circulating tumor DNA (ctDNA) to monitor disease interrogated only one or a few genes and failed to develop workable criteria to inform clinical practice. We evaluated the feasibility of detecting resistance to anti-HER2 therapy by serial gene-panel ctDNA sequencing. RESULTS: Primary therapeutic resistance was identified in 6 out of 14 patients with events of progressive disease. For this subset comparison of pre- and post-treatment ctDNA assay results revealed that HER2 amplification concurred with disease progression (4/6, 66...
September 1, 2016: Oncotarget
F Pietrantonio, M Caporale, F Morano, M Scartozzi, A Gloghini, F De Vita, E Giommoni, L Fornaro, G Aprile, D Melisi, R Berenato, A Mennitto, C C Volpi, M M Laterza, V Pusceddu, L Antonuzzo, E Vasile, E Ongaro, F Simionato, F de Braud, V Torri, M Di Bartolomeo
Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score <3+ and absence of ISH amplification, and IHC "downscoring" from 2+/3+ to 0/1+, respectively...
December 15, 2016: International Journal of Cancer. Journal International du Cancer
John O Richards, Alex J Albers, Thomas S Smith, Judy A Tjoe
Tumor-targeting antibodies have been successful in the treatment of various types of cancers. Antibodies engage the immune system with their Fc, stimulating immune cell effector function. In the clinic, FcγRIIIa polymorphisms with higher affinity for the Fc of antibodies were shown to improve response rates and overall survival. Efforts have been made to modify the Fc to enhance affinity to Fc receptors and thereby improve effector function. An alternative for improving immune effector function may be to increase the level of tumor antigen expression...
August 29, 2016: Cancer Immunology, Immunotherapy: CII
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