A case-matched comparison of ER-α and ER-β expression between malignant and benign cystic pancreatic lesions

Abstract Objectives Older studies failed to establish a link between estrogen receptor (ER) expression and pancreatic adenocarcinoma, with findings either statistically insignificant or contradictory. The recent discovery of two distinct isoforms, namely ER-α and ER-β, with potentially differential expression in various pancreatic cells and with radically different effects, might explain preexisting contradictions. Therefore, the identification of two new ER types necessitates a reassessment of their role in the development and prognosis of pancreatic adenocarcinoma. This study aimed to investigate their differential expression in benign and malignant pancreatic lesions. Methods A case-matched study was conducted comparing benign and malignant pancreatic lesions in patients who underwent surgery at University Hospital ‘Aretaieio’, a tertiary referral centre for pancreatic disease. The expression of ER-α and ER-β receptors was assessed by immunohistochemistry and scored using two established scoring systems. Data regarding age, gender, histological diagnosis, grade, TNM stage, adjuvant treatment, follow-up, recurrence, and survival were recorded, and respective correlations were assessed. Results ER-α was detected in 31.25 % of benign tumours but not in any malignant tumours (p=0.003). ER-β was positive in 31.25 % of benign and 37.50 % of malignant tumours (p=0.757). Disease-free survival (p=0.910) and overall survival (p=0.623) were similar between ER-β negative and ER-β positive patients. Conclusions Pancreatic adenocarcinomas do not express ER-α, which might explain the failure of earlier trials targeting these receptors, but they do express ER-β at a considerable rate. Differences in the expression of ER-α and ER-β can be used to distinguish benign and malignant lesions. Moreover, further studies delineating the molecular function of ER-β and assessing it as a potential therapeutic target can lead to improved clinical outcomes.