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Jennifer R Eads Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Pennsylvania, USA

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Thorvardur R Halfdanarson Division of Medical Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA

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Tim Asmis Division of Medical Oncology, University of Ottawa, Ottawa, Ontario, Canada

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Andrew M Bellizzi Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA

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Emily K Bergsland Department of Medicine, University of California, San Francisco, California, USA

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Arvind Dasari Division of Gastrointestinal Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Ghassan El-Haddad Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

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Michael Frumovitz Division of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Joshua Meyer Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

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Erik Mittra Division of Molecular Imaging and Therapy, Oregon Health & Science University, Portland, Oregon, USA

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Sten Myrehaug Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Eric Nakakura Department of Surgery, University of California, San Francisco, California, USA

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Nitya Raj Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Heloisa P Soares Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Salt Lake City, Utah, USA

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Brian Untch Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA

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Namrata Vijayvergia Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

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Jennifer A Chan Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Introduction High-grade neuroendocrine neoplasms (NENs) constitute a rare disease entity and account for approximately 10% of all NENs. Given their rarity, there is a paucity of prospective data to guide the optimal diagnosis and management of

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Andreas Venizelos K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Hege Elvebakken Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway

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Aurel Perren Institute of Pathology, University of Bern, Bern, Switzerland

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Oleksii Nikolaienko K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Wei Deng K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Inger Marie B Lothe Department of Pathology, Oslo University Hospital, Oslo, Norway

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Anne Couvelard Department of Pathology, Université de Paris, Bichat Hospital, AP-HP, Paris, France

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Geir Olav Hjortland Department of Oncology, Oslo University Hospital, Oslo, Norway

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Anna Sundlöv Departmentt of Oncology, Skåne University Hospital, Lund, Sweden
Department of Medical Radiation Physics, Lund University, Lund, Sweden

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Johanna Svensson Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden

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Harrish Garresori Department of Oncology, Stavanger University Hospital, Stavanger, Norway

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Christian Kersten Department of Research, Hospital of Southern Norway, Kristiansand, Norway

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Eva Hofsli Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Department of Oncology, St.Olavs Hospital, Trondheim, Norway

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Sönke Detlefsen Department of Pathology, Odense University Hospital, Odense, Denmark
Department of Clinical Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Merete Krogh Department of Oncology, Odense University Hospital, Odense, Denmark

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Halfdan Sorbye Department of Oncology, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, University of Bergen, Bergen, Norway

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Stian Knappskog K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Introduction High-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are defined by the presence of neuroendocrine phenotype and a high proliferation rate (Ki-67 > 20%). The HG NEN entity consists of well

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Andreas Venizelos K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Halfdan Sorbye Department of Oncology, Haukeland University Hospital, Bergen, Norway
Department of Clinical Science, University of Bergen, Bergen, Norway

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Hege Elvebakken Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway

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Aurel Perren Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland

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Inger Marie B Lothe Department of Pathology, Oslo University Hospital, Oslo, Norway

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Anne Couvelard Department of Pathology, Université Paris Cité and AP-HP, Bichat Hospital, Paris, France

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Geir Olav Hjortland Department of Oncology, Oslo University Hospital, Oslo, Norway

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Anna Sundlöv Departmentt of Oncology, Skåne University Hospital, Lund, Sweden
Department of Medical Radiation Physics, Lund University, Lund, Sweden

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Johanna Svensson Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden

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Harrish Garresori Department of Oncology, Stavanger University Hospital, Stavanger, Norway

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Christian Kersten Department of Research, Hospital of Southern Norway, Kristiansand, Norway

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Eva Hofsli Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Department of Oncology, St. Olavs Hospital, Trondheim, Norway

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Sönke Detlefsen Department of Pathology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark

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Lene W Vestermark Department of Oncology, Odense University Hospital, Odense, Denmark

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Morten Ladekarl Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark

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Elizaveta Mitkina Tabaksblat Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark

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Stian Knappskog K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Oncology, Haukeland University Hospital, Bergen, Norway

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Introduction Neuroendocrine neoplasms (NENs) constitute ~2% of all malignancies and are frequently located in the gastrointestinal (GI) tract and pancreas. High-grade gastroenteropancreatic (HG-GEP) NENs are among the most aggressive cancers

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Alicia A Tone The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9
The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9
The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9
The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9

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Carl Virtanen The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9

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Patricia A Shaw The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9
The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9
The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9

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Theodore J Brown The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9
The Samuel Lunenfeld Research Institute, Department of Laboratory Medicine and Pathobiology, Department of Obstetrics and Gynecology, Department of Pathology, Microarray Centre, Mount Sinai Hospital, University of Toronto, 60 Murray Street, PO Box 41, Toronto, Ontario, Canada M5T 3L9

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epithelium (OSE), accumulating evidence provides strong support that high-grade serous adnexal cancer, commonly attributed to an ovarian origin, arises from the distal fallopian tube epithelium (FTE; Colgan et al . 2001 , Piek et al . 2001 , Finch et al

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Catherine T Choy Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Haseong Kim Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Ji-Young Lee Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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David M Williams Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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David Palethorpe Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Greg Fellows Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Alan J Wright Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Ken Laing Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Leslie R Bridges Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Franklyn A Howe Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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Soo-Hyun Kim Division of Biomedical Sciences, Academic Neurosurgery Unit, Division of Clinical Sciences, Department of Cellular Pathology, Division of Cardiac and Vascular Sciences, Department of Electrical and Electronic Engineering, St George's Medical School, University of London, Cranmer Terrace, London SW17 0RE, UK

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that KAL1 was differentially expressed according to the grade and type of tumor, showing an upregulation in high-grade primary brain tumors. We also found that anosmin-1 enhanced proliferation and motility of glioblastoma cells in vitro , formed a

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Siker Kimbung Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Sweden

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Ching-yi Chang Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA

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Pär-Ola Bendahl Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Sweden

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Laura Dubois Duke Proteomics and Metabolomics Resource, Duke University School of Medicine, Durham, NC, USA

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J Will Thompson Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA
Duke Proteomics and Metabolomics Resource, Duke University School of Medicine, Durham, NC, USA

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Donald P McDonnell Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA

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Signe Borgquist Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Sweden
Clinical Trial Unit, Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden

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seen among high-grade tumors ( Nelson et al. 2013 ). In addition, the concentration of 27HC was found to be higher in ERα-positive breast tumors compared to normal breast tissue, and this was attributed to a corresponding decrease in the expression of

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N Burrows School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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J Resch School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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R L Cowen School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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R von Wasielewski School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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C Hoang-Vu School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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C M West School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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K J Williams School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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G Brabant School of Pharmacy and Pharmaceutical Sciences, Department of Endocrinology, Department of Pathology, Experimental and Surgical Oncology, Academic Department of Radiation Oncology, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK

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thyroid tumours, the effect on radiation resistance is of high therapeutic relevance in these aggressive carcinomas. Previous data characterizing the potential role of HIF-1α in thyroid carcinomas are limited. In vitro studies have shown that

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Louis W C Chow State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau SAR, Macao
Organisation for Oncology and Translational Research, Hong Kong SAR, China
UNIMED Medical Institute, Hong Kong SAR, China

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Satoshi Morita Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan

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Christopher Y C Chow UNIMED Medical Institute, Hong Kong SAR, China

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Wai-Kuen Ng Department of Pathology, Precious Blood Hospital, Hong Kong SAR, China

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Masakazu Toi Organisation for Oncology and Translational Research, Hong Kong SAR, China
Breast Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

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Introduction The usefulness of endocrine therapy has been well demonstrated in the management of hormone-sensitive breast cancer ( Ellis et al. 2011 ). The neoadjuvant ACOSOG Z1031 trial showed a high clinical response rate of 63–75% in

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Anna Koumarianou Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Stavroula Antoniou Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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George Kanakis Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Nikolaos Economopoulos Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dimitra Rontogianni Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Anastasios Ntavatzikos Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Nikolaos Tsavaris Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dimitrios Pectasides Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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George Dimitriadis Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Gregory Kaltsas Medical Oncology Unit, Endocrine Unit, MRI Unit, Pathology Department, Fourth Department of Surgery, Medical Oncology Unit, Second Department of Internal Medicine Propaedeutic, Attikon University General Hospital, Rimini 1, 12462 Athens, Greece

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Dear Editor Neuroendocrine tumours (NETs) are highly vascularised tumours that express high levels of the vascular endothelial growth factor (VEGF) ligand together with its receptor VEGFR ( Modlin et al . 2008 ). Although advanced NETs may exhibit

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Sung Gwe Ahn Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Chang Ik Yoon Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Jae Hoon Lee Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Hye Sun Lee Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea

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So Eun Park Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Yoon Jin Cha Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Chihwan Cha Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Soong June Bae Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Kyung-A Lee Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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Joon Jeong Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

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-positive/HER2-negative tumors, similar to high Ki67 level or poor histologic grade. Our findings are in line with those of previous studies indicating that the loss of PR expression correlates with aggressive tumor characteristics ( Arpino et al . 2005

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