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Pozios, Ioannis; Knoesel, Thomas; Zhao, Yue; Assmann, Gerald; Pozios, Iraklis; Müller, Mario H.; Bruns, Christiane J.; Kreis, Martin E.; Seeliger, Hendrik (2018): Expression of phosphorylated estrogen receptor beta is an independent negative prognostic factor for pancreatic ductal adenocarcinoma. In: Journal of Cancer Research and Clinical Oncology, Vol. 144, No. 10: pp. 1887-1897
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Abstract

The role of estrogen receptor beta (ER-beta) expression in pancreatic ductal adenocarcinoma (PDAC) is largely unknown. Ligand-independent phosphorylation and activation of ER-beta may play a relevant role in the IL-6/STAT3 signaling pathway and, as a result, in tumor progression. Here, we examined the effect of ER-beta, phosphorylated ER-beta (pER-beta), STAT3, phosphorylated STAT3 (pSTAT3) and IL-6 expression on the overall and recurrence-free survival in a cohort of patients with resected PDAC. We identified 175 patients who underwent pancreatic resection for PDAC. Tissue microarrays were constructed from the archival tumor specimens. These were stained with specific antibodies for the above molecules. The expression of the markers was then correlated with clinicopathological parameters and survival analysis was performed. High nuclear expression of ER-beta was found in 61.7% and pER-beta in 80.6% of the tumors. STAT3 was expressed in 54.3% of the tumor samples, pSTAT3 in 68% and IL-6 in 76.6%. The median overall survival for patients with low pER-beta expression was 29 months, whereas for patients with high pER-beta expression was 15.1 months (p = 0.016). Multivariate analysis revealed that pER-beta expression was an independent factor correlating with shorter overall survival (hazard ratio 1.9;p = 0.013) and disease-free survival (hazard ratio 1.9;p = 0.029). Expression of pER-beta constitutes an independent prognostic marker for PDAC and is correlated with poor prognosis. These data may help in identifying novel drug targets in PDAC and patients who could benefit from additional therapeutic regimens, including selective estrogen receptor modulators.