The most striking epidemiological feature of Oesophageal adenocarcinoma (OAC) is its strong unexplained male predominance, suggesting a protective effect for oestrogens, but few studies have investigated expression of sex hormone receptors in OAC. In a retrospective cohort of OAC patients, we evaluated Oestrogen Receptor (ER) α and β and Androgen Receptor (AR) tumour expression and investigated associations with OAC recurrence and survival.Methods
We identified 148 OAC patients who underwent neo-adjuvant chemotherapy prior to surgical resection between 2004–2012 at the Northern Ireland Cancer Centre. Immunohistochemical expression of ERα, ERβ and AR was scored by two independent observers, blinded to the clinical data. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations between sex hormone receptor expression and overall survival, cancer-specific survival and recurrence-free survival. All analyses were adjusted for clinic-pathological and lifestyle factors including age at diagnosis, sex, pathological nodal stage, primary site, lymphovascular invasion, circumferential margin involvement, PET response and smoking. Sub-group analysis was conducted by Siewert classification.Results
Weak positive expression was identified for ERα (6/139) and AR (4/138) while moderate positive expression was observed for ERβ (43/138). After a mean follow-up of 3 years (max 9 years), no significant associations were observed for ERα, ERβ or AR expression and OAC recurrence or survival. ERβ expression however was associated with significant improvements in overall survival (HR 0.38, 95% CI 0.16, 0.88), cancer-specific survival (HR 0.36, 95% CI 0.15, 0.84) and recurrence-free survival (HR 0.28, 95% CI 0.12, 0.69) in patients with adenocarcinoma of the distal oesophagus (Siewert type I).Conclusion
In the largest study to date, we found little evidence of ERα or AR expression in OAC. We observed moderate expression of ERβ and suggestive evidence that its expression was associated with reduced recurrence and death in patients with adenocarcinoma of the distal oesophagus. Further studies however are required to replicate our findings to determine if the ER system could be a potential prognostic biomarker in OAC.