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Anticancer Res ; 38(7): 3863-3870, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29970506

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%

Subject(s)
Cell Cycle Proteins/metabolism , Gastrointestinal Neoplasms/metabolism , Mitosis , Neuroendocrine Tumors/metabolism , Pancreatic Neoplasms/metabolism , Aurora Kinase B/metabolism , Biomarkers, Tumor/metabolism , Female , Forkhead Box Protein M1/metabolism , Gastrointestinal Neoplasms/pathology , Humans , Immunohistochemistry , Inhibitor of Apoptosis Proteins/metabolism , Male , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Survivin
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