Expression of estrogen receptor beta correlates with adverse prognosis in resected pancreatic adenocarcinoma

Hendrik Seeliger,Christiane J Bruns,Martin E Kreis,Gerald Assmann,Mario H Müller,Ioannis Pozios,Thomas Knösel,Yue Zhao

doi:10.1186/s12885-018-4973-6

Abstract

BackgroundThe relevance of estrogen receptor (ER) expression in pancreatic ductal adenocarcinoma (PDAC) is largely unknown. Clinical trials targeting ER with selective estrogen receptor modulators in pancreatic cancer did not show any benefit. Here, we analyze the impact of recently characterized ER isoform beta on survival in a cohort of patients with resected PDAC.MethodsEighty-four patients having undergone pancreatic resection for PDAC at a single institution were identified. Tissue microarrays were constructed of archival tumor specimens. The expression of ER beta was determined by immunohistochemistry and quantified by a system established for estrogen receptor expression in breast cancer. ER beta expression was then correlated with clinicopathological parameters, and univariate and multivariate survival analyses were performed.ResultsNuclear expression of ER beta was found in 31% of tumors. No significant correlation was found between ER beta expression and TNM status, tumor grade, age or sex. Univariate analysis revealed nodal metastasis and the expression of ER beta as factors correlating with a shorter overall survival and disease free survival. When comparing ER beta expression in patients surviving more than 24 months with those who died from the tumor within 12 or 24 months, respectively, a significantly lower ER beta expression was found in the long term survivors. In multivariate analysis, ER beta expression was demonstrated to be an independent predictor of shorter overall survival.ConclusionsIn resected PDAC, expression of ER beta seems to correlate with poor prognosis. These data may help to identify patients who may benefit from additional systemic therapy including selective estrogen receptor modulators.

Highlights

The relevance of estrogen receptor (ER) expression in pancreatic ductal adenocarcinoma (PDAC) is largely unknown
Patients We identified 111 consecutive patients from a prospective database of patients operated for ductal pancreatic adenocarcinoma at a single institution
Expression of ERβ A nuclear expression of the ERβ was detected in 26 PDAC tumor specimens (31.0%)

Summary

Introduction

The relevance of estrogen receptor (ER) expression in pancreatic ductal adenocarcinoma (PDAC) is largely unknown. Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related mortality in western countries [1]. Standard therapeutic regimens consist of surgery, cytotoxic chemotherapy, Seeliger et al BMC Cancer (2018) 18:1049 safety profile [12,13,14]. This concept of inhibition of ER mediated effects did not take into account recently reported existence of differential signaling of ER isoforms ERα and ERβ [15,16,17]. While ERα was demonstrated to promote tumor growth and angiogenesis in breast cancer and many other solid tumor types, the role of ERβ is defined much less clearly

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