ECE2016 Eposter Presentations Endocrine tumours and neoplasia (68 abstracts)
1Charité, Berlin, Germany; 2Department of Chemistry and Biochemistry, Freie Universität (FU), Berlin, Germany; 3Zentralklinik bad Berka, Bad Berka, Germany; 4Klinikum Friedrichshafen, Friedrichshafen, Germany; 5Vivantes Klinikum Friedrichshain, Berlin, Germany.
Objective: Gastroenteropancreatic neuroendocrine neoplasm (GEP-NENs) are rare and heterogeneous in their tumor biology. Therapeutic options to prevent growth and dissemination are still not satisfactory. As shown previously, survivin and aurora kinases (members of the mitotic chromosomal passenger complex) play a role in cell cycle progression; FOXM1 is a transcription factor that regulates G2/M progression and is associated with grading and metastasis in GEP-NENs. Aurora kinases, survivin and Ki-67 have been described as transcriptional targets of FOXM1. Here, we immunohistochemically analyzed this protein network as potential tumor markers.
Methods: Tumor tissues from 128 patients were studied immunohistochemically with anti-survivin, anti-FOXM1, anti-STAT3, and AIM 1 (auroraB) antibody (>5%: positive). The expression pattern war correlated with follow up data such as tumor progression, time of death and cause of death.
Results: The immunohistochemical analysis of auroraB revealed an association with survivin, as both nuclear scores were positively correlated (P=0.000). We further found associations with the expression of STAT3. AuroraB-expression was related to high FOXM1 expression (P=0.046). In accordance with the strong association of survivin/FOXM1 expression with grading and differentiation, we found cytosolic AuroraB almost exclusively in G1/G2 tumors, nuclear AuroraB expression in G3 tumors (both: P=0.000).
Conclusion: Our study shows that the expression of AuroraB is associated with differentiation, progression and aggressiveness of GEP-NENs. The association of AuroraB with STAT3, which is involved in tumor-stroma communication, deserves further investigation. AuroraB is strongly associated with other markers of the mitosis regulatory network, including survivin, FOXM1 and Ki-67. We therefore propose to include this set of proliferation markers into routine diagnostics in order to individualize therapeutic strategies in this tumor entity in the future.