RT Journal Article
SR Electronic
T1 Immunohistochemical Study of Mitosis-regulatory Proteins in Gastroenteropancreatic Neuroendocrine Neoplasms
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3863
OP 3870
DO 10.21873/anticanres.12670
VO 38
IS 7
A1 FRANZISKA BRIEST
A1 YAWEN WANG
A1 RUZA ARSENIC
A1 SEFER ELEZKURTAJ
A1 ERIKA BERG
A1 SONJA GRESHAKE
A1 ADRIAN C. LOCK
A1 DIETER HÖRSCH
A1 CHRISTIAN N. ARNOLD
A1 MICHAEL HUMMEL
A1 BRITTA SIEGMUND
A1 PATRICIA GRABOWSKI
YR 2018
UL http://ar.iiarjournals.org/content/38/7/3863.abstract
AB 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.