Expression And Prognosis Of ER_α And GPER In Pancreatic Carcinoma

Background and PurposeIncidence of pancreatic carcinoma (PaCa) was imbalance betweenmale and female. Therefore, estrogen was presumed to play a potential rolein pancreatic tumorigenesis, while the expression and significance ofestrogen and estrogen receptors（ER）were controversial. Functionally,G-Protein Coupled estrogen receptor1（GPER）transactivated epidermalgrowth factor receptor (EGFR) and its downstream signaling pathway inresponse to stimulus, up-regulating the expression of a set of proteins, suchas connective tissue growth factor (CTGF), and facilitating fibronectin (FN)matrix assembly, and contributed to promote cellular proliferation,invasiveness and migration. Interestingly, GPER was expressed in normalpancreatic tissues and correlated with the endocrine function of pancreas.However, the significance of GPER and its signal pathway in pancreaticcancer were not reported in the available references. Aim of this study wasto investigate the potential role of ERα, GPER and its signal pathway inpancreatic carcinoma.MethodsThe expression of ERα, GPER, EGFR, CTGF and FN were detected by immunohistochemical analysis in39paraffin-embedded tissues ofpancreatic carcinoma. The correlation between their expression andclinicopathological variables and patients’ survival was evaluated.ResultsERα was positive in59.0%of the tumor tissues investigated. Therewas significant association between ERα expression and vascular invasion.GPER was expressed in most of pancreatic tumors (77.4%). GPERimmunostaining correlated significantly with patient age, vascular invasionand the expression of EGFR, CTGF and FN. EGFR, CTGF and FN wereexpressed in33.3%,46.2%and53.8%of the samples, while there was nosignificant relationship between their expression and clinicopathologicalvariables. The median follow-up time of the study population was7.7months (range from2.2to42.0months). In survival analysis, significantcorrelation was observed between ERα expression and overall survival(median:8.3versus6.1months P=0.019). GPER expression was associatedwith better overall survival (median:8.0versus6.1months), but thisdiscrepancy without statistical significance (P=0.054). Meanwhile, nosignificant association was observed between overall survival and theexpression of EGFR, CTGF and FN. Univariate analysis revealed thatGPER (HR,0.454; P=0.043) and ERα (HR,0.457; P=0.031) wereprotective prognostic factors for PaCa. Tumor location (HR,2.719;P=0.019), lymph node invasion (HR,2.671; P=0.009) and vascular invasion (HR,2.112; P=0.033) were unfavourable prognostic parameters.No significant correlation was detected between overall survival and otherclinicopathological variables (patient sex, tumor size, histological type,tumor differentiation, tumor staging). Multivariate analysis demonstratedthat all the clinicopathological determinants were not independentprognostic factors except for tumor differentiation (HR,3.519; P=0.022).ConclusionERα and GPER expression were negatively associated with vascularinvasion and regarded as favourable prognostic parameters. Estrogen mayplay a potential protective role in pancreatic neoplasm through ERα andGPER. ERα and GPER could be potential targets for pancreatic carcinoma,while their biological function and significance have to be furtherinvestigated.