Probing the link between oestrogen receptors and oesophageal cancer

BACKGROUND Human oesophageal carcinoma is considered to be one of the most aggressive malignancies and has a very poor prognosis. The incidence of oesophageal cancer shows a gender bias and is higher in males compared with females, the ratio between males and females varying from 3:1 to 7:1. This sex ratio is not entirely attributable to differences in the prevalence of known risk factors between the sexes. The potential role of oestrogen receptors (ER) in oesophageal cancer has been debated for several years but the significance of the receptors in this cancer remains unknown. Most of the work has been based on immunohistochemistry and has not been validated with other available techniques. The inconsistencies in the published literature on the link between ER expression and oesophageal cancer warrant a thorough evaluation of the potential role of ERs in this malignancy. Even the expression of the two ER isoforms, ERalpha and ERbeta, and its implications for outcome of treatments in histological subtypes of oesophageal tumours is ill defined. The aim of this article is to provide updated information from the available literature on the current status of ER expression in oesophageal cancer and to discuss its potential therapeutic role. METHODS AND RESULTS We performed a comprehensive literature search and analysed the results regarding ER expression in oesophageal tumours with special emphasis on expression of different oestrogen receptors and the role of sex hormones in oesophageal cancer. This article also focuses on the significance of the two main ER subtypes and mechanisms underlying the presumed male predominance of this disease. CONCLUSION We postulate that differential oestrogen receptor status may be considered a biomarker of poor clinical outcome based on tissue dedifferentiation or advanced stage of the disease. Further, if we can establish the importance of oestrogen and its receptors in the context of oesophageal cancer, then this may lead to a new future direction in the management of this malignancy.