Expression of estrogen receptor beta isoforms in pancreatic adenocarcinoma.

Abstract

337 Background: There have been several limited trials in which tamoxifen efficacy was tested in patients with pancreatic adenocarcinoma (PAC). Most of these studies were small series of patients with unresectable PAC and reported mixed results. In these studies, patients were not stratified by estrogen receptor status because estrogen receptor beta (ER-b) had not yet been identified, and PAC did not express the traditional ER-alpha. Recent studies showed that the effects of estrogens, phytoestrogens and tamoxifen on PAC cell lines depended on ER-b expression. The aim of this study was to investigate ER-b expression in human PAC and whether such expression correlates with any clinicopathologic parameters. Methods: Sections of tissue microarray containing 18 formalin fixed and paraffin embedded human PAC were stained by immunohistochemistry (IHC) using monoclonal antibodies to ER-b isoforms 1, 2, and 5 (ER-b1, ER-b2, and ER-b5, respectively), and for Cyclin A. The levels of ER-b isoform expression in tumor cells and the S-phase fraction (SPF) were determined using a quantitative digital image analysis solution (OTMIAS). Results: All isoforms were expressed in PAC, although at different levels. Higher mean ER-b2 levels correlated with male sex (p = 0.057), older age (p = 0.005), and lower pT stage (p = 0.008), but not with grade, pN stage, or SPF. Mean ER-b5 levels correlated negatively with SPF (p = 0.021), but not with sex, age, grade, pT or pN. Mean ER-b1 expression did not correlate with any of the above mentioned clinicopathologic factors. Conclusions: ER-b1, ER-b2, and ER-b5 are expressed in PAC. Higher ER-b2 and ER-b5 levels of expression are significantly correlated with lower tumor pT stage and with lower SPF, respectively, suggesting that they may play a tumor suppressive role in PAC. The association between ER-b2 levels and patient sex and age suggest that it could be influenced by endogenous/exogenous hormonal exposure.