Franziska Briest1,2, Yawen Wang3,4, Ruza Arsenic5, Sefer Elezkurtaj5, Erika Berg5, Sonja Greshake3, Adrian C Lock3, Dieter Hörsch2, Christian N Arnold6, Michael Hummel5, Britta Siegmund3, Patricia Grabowski3,2,7. 1. Department of Gastroenterology, Infectious Diseases and Rheumatology, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany franziska.briest@charite.de. 2. Department of Gastroenterology and Endocrinology, Zentralklinik Bad Berka GmbH, Bad Berka, Germany. 3. Department of Gastroenterology, Infectious Diseases and Rheumatology, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 4. Department of Neurosurgery, Vivantes Klinikum im Friedrichshain, Berlin, Germany. 5. Institute of Pathology, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 6. Klinikum Friedrichshafen, Department of Gastroenterology, Friedrichshafen, Germany. 7. Department of Medical Immunology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Abstract
BACKGROUND/AIM: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and heterogeneous tumors. Therapeutic targets remain to be identified and apart from the proliferation marker Ki-67, useful prognostic markers are rare. Mitotic proteins, such as forkheadbox protein M1 (FOXM1), survivin and aurora kinases, play a role in GEP-NEN progression. In this study, immunohistochemistry was used to analyze how this protein network is expressed in different subgroups of GEP-NENs and determine potential expression patterns that could be useful as tumor markers. MATERIALS AND METHODS: Tumor tissues from 75 patients were studied immunohistochemically with antibodies against aurora B, survivin and FOXM1. The expression pattern was correlated with clinicopathological data such as tumor grading, metastatic state and prognosis. RESULTS: The immunohistochemical analysis of nuclear aurora kinase B revealed a positive correlation with nuclear survivin and FOXM1 staining patterns. Furthermore, aurora B was positively related to grading and tumor size and negatively to differentiation and functionality. CONCLUSION: The expression of aurora kinase B is associated with differentiation, progression and the aggressiveness of GEP-NENs. In the context of tumor progression, aurora B is strongly associated with markers of the mitosis regulatory network, survivin, FOXM1 and Ki-67. A shift of the intracellular localization of aurora B might be useful for the subclassification of intermediate-grade intestinal NET and NEC (20%<Ki-67<55%), since detailed Ki-67-based guidelines only exist for the pancreatic tumors. Most importantly, nuclear abundance of aurora B was found to be strictly limited to high-grade tumors, which is important for the consideration of aurora inhibitors for therapy of NENs. Copyright
BACKGROUND/AIM: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and heterogeneous tumors. Therapeutic targets remain to be identified and apart from the proliferation marker Ki-67, useful prognostic markers are rare. Mitotic proteins, such as forkheadbox protein M1 (FOXM1), survivin and aurora kinases, play a role in GEP-NEN progression. In this study, immunohistochemistry was used to analyze how this protein network is expressed in different subgroups of GEP-NENs and determine potential expression patterns that could be useful as tumor markers. MATERIALS AND METHODS:Tumor tissues from 75 patients were studied immunohistochemically with antibodies against aurora B, survivin and FOXM1. The expression pattern was correlated with clinicopathological data such as tumor grading, metastatic state and prognosis. RESULTS: The immunohistochemical analysis of nuclear aurora kinase B revealed a positive correlation with nuclear survivin and FOXM1 staining patterns. Furthermore, aurora B was positively related to grading and tumor size and negatively to differentiation and functionality. CONCLUSION: The expression of aurora kinase B is associated with differentiation, progression and the aggressiveness of GEP-NENs. In the context of tumor progression, aurora B is strongly associated with markers of the mitosis regulatory network, survivin, FOXM1 and Ki-67. A shift of the intracellular localization of aurora B might be useful for the subclassification of intermediate-grade intestinal NET and NEC (20%<Ki-67<55%), since detailed Ki-67-based guidelines only exist for the pancreatic tumors. Most importantly, nuclear abundance of aurora B was found to be strictly limited to high-grade tumors, which is important for the consideration of aurora inhibitors for therapy of NENs. Copyright
Authors: Chandra K Maharjan; Po Hien Ear; Catherine G Tran; James R Howe; Chandrikha Chandrasekharan; Dawn E Quelle Journal: Cancers (Basel) Date: 2021-10-12 Impact factor: 6.639
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Authors: Sarabjot Pabla; Jeffrey M Conroy; Mary K Nesline; Sean T Glenn; Antonios Papanicolau-Sengos; Blake Burgher; Jacob Hagen; Vincent Giamo; Jonathan Andreas; Felicia L Lenzo; Wang Yirong; Grace K Dy; Edwin Yau; Amy Early; Hongbin Chen; Wiam Bshara; Katherine G Madden; Keisuke Shirai; Konstantin Dragnev; Laura J Tafe; Daniele Marin; Jason Zhu; Jeff Clarke; Matthew Labriola; Shannon McCall; Tian Zhang; Matthew Zibelman; Pooja Ghatalia; Isabel Araujo-Fernandez; Arun Singavi; Ben George; Andrew Craig MacKinnon; Jonathan Thompson; Rajbir Singh; Robin Jacob; Lynn Dressler; Mark Steciuk; Oliver Binns; Deepa Kasuganti; Neel Shah; Marc Ernstoff; Kunle Odunsi; Razelle Kurzrock; Mark Gardner; Lorenzo Galluzzi; Carl Morrison Journal: J Immunother Cancer Date: 2019-02-01 Impact factor: 13.751