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

Abstract

Background: The 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.

Methods: Eighty-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.

Results: Nuclear 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.

Conclusions: In 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.

Keywords: Estrogen receptor beta; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Prognosis; Survival analysis; Tissue microarray.

Fig. 1

Nuclear expression of estrogen receptor beta (ERβ) in pancreatic ductal adenocarcinoma and corresponding normal tissue. Samples of nontumorous pancreatic tissue (upper panel) and corresponding pancreatic ductal adenocarcinoma (lower panel) without (a and c) and with ERβ expression (b and d) are shown. ERβ immunohistochemistry, magnification 640× (a-d)

Fig. 2

Analysis of overall survival and disease free survival in 84 patients with resected pancreatic ductal adenocarcinoma

Fig. 3

Estrogen receptor beta (ERβ) expression in ductal pancreatic adenocarcinoma. Percentages of ERβ expressing tumors are shown by stratification into tumor dependent death after less than 12 and more than 12 but less than 24 months, and overall survival more than 24 months. Significantly fewer tumors of long-term overall survivors expressed ERβ, compared to other strata (p = 0.043, < 24 months versus 12–24 months; p = 0.0026, > 24 months versus < 12 months; p = 0.000099, > 24 months versus < 24 months)