RT Journal Article SR Electronic T1 Endoplasmic Reticulum Stress in Pancreatic Neuroendocrine Tumors is Linked to Clinicopathological Parameters and Possible Epigenetic Regulations JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6127 OP 6136 VO 35 IS 11 A1 ECKHARD KLIESER A1 ROMANA ILLIG A1 STEFAN STÁTTNER A1 FLORIAN PRIMAVESI A1 TARKAN JÁGER A1 STEFAN SWIERCZYNSKI A1 TOBIAS KIESSLICH A1 RALF KEMMERLING A1 CARMEN BOLLMANN A1 PIETRO DI FAZIO A1 DANIEL NEUREITER YR 2015 UL http://ar.iiarjournals.org/content/35/11/6127.abstract AB Background: Endoplasmic reticulum (ER) stress is a highly-conserved cellular defense mechanism in response to perturbations of ER function. The role of ER stress in pancreatic neuroendocrine tumors (pNET) still remains unclear. Materials and Methods: We analyzed the protein expression pattern of the four key players of ER stress, (chaperone binding imunoglobluin protein (BiP), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4) and caspase 4) as well as histone deacetylases (HDACs) by a tissue microarray (TMA) of 49 human pNET resected between 1997 and 2013 following, extensive clinicopathological characterization. Results: Immunohistochemical profiling revealed a significant up-regulation of BiP, ATF4, CHOP and caspase 4 in pNET cases compared to normal controls. Correlated to clinicopathological parameters especially BiP expression could be linked to higher grading and proliferation as well as to lower survival probability. Finally, expression of ER stress markers correlated with HDAC expression in situ and pharmalogical inhibition by panobinostat significantly reduced cell viability in vitro. Conclusion: Up-regulation of ER stress in pNET indicates the presence and engagement of ER stress signaling in this tumor entity demonstrating another possible anticancer therapy option in pNET.