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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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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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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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Takeshi Ujike Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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Motohide Uemura Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Department of Therapeutic Urologic Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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Atsunari Kawashima Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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Akira Nagahara Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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Kazutoshi Fujita Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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Yasushi Miyagawa Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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Norio Nonomura Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

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examining 354 patients undergoing robot-assisted prostatectomy, they concluded that low FT levels were linked with high-grade prostate cancer. In total, the relationship between prostate cancer risk and absolute androgen concentration remain controversial

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Jonathan R Strosberg Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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James C Yao Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Emilio Bajetta Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Mounir Aout Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Bert Bakker Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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John D Hainsworth Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Philippe B Ruszniewski Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Eric Van Cutsem Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Kjell Öberg Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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Marianne E Pavel Department of Medicine, Division of Cancer Medicine, Istituto di Oncologia, Novartis International AG, Novartis Pharmaceuticals Corporation, Sarah Cannon Research Institute, University of Paris VII and Beaujon Hospital, Digestive Oncology, Uppsala University Hospital, Department of Hepatology and Gastroenterology, Moffitt Cancer Center, Tampa, Florida, USA

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differentiated or high-grade NET were not eligible. Furthermore, patients were ineligible if they had received cytotoxic chemotherapy, immunotherapy, or radiotherapy within 4 weeks prior to randomization, or prior therapy with mammalian target of rapamycin

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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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Maria Angela De Stefano Department of Public Health, University of Naples “Federico II”, Naples, Italy

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Tommaso Porcelli Department of Public Health, University of Naples “Federico II”, Naples, Italy

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Martin Schlumberger Department of Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

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Domenico Salvatore Department of Public Health, University of Naples “Federico II”, Naples, Italy
CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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et al. 2012 ), we showed that D3 is dramatically downregulated at later phases of tumorigenesis and that the expression of D2 is upregulated in high-grade squamous cell carcinoma. High D2 expression levels have also been found in other advanced

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Sara Pusceddu Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Francesco Barretta Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy

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Annalisa Trama Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Evaluative Epidemiology Unit, ENETS Center of Excellence, Milan, Italy

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Laura Botta Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Evaluative Epidemiology Unit, ENETS Center of Excellence, Milan, Italy

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Massimo Milione Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ENETS Center of Excellence, Milan, Italy

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Roberto Buzzoni Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

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Filippo De Braud Department of Medical Oncology ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
University of Milan, Milan, Italy

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Vincenzo Mazzaferro University of Milan, Milan, Italy
Liver Surgery, Transplantation and Gastroenterology, University of Milan and Istituto Nazionale Tumori Fondazione IRCCS, ENETS Center of Excellence, Milano, Milan, Italy

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NEPscore Working Group
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scores for OS have been specifically developed to assess OS in patients with gut NETs ( Modlin et al . 2010 ) or gastrointestinal high-grade, G3 neuroendocrine carcinomas (GI-NECs) ( Lamarca et al . 2017 ), to predict progression-free survival of

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