Why oesophageal adenocarcinoma occurs approximately 8 times less often in women than men is not well understood. One possiblity is that oestrogen and its receptors play a role. This study investigated the difference in expression levels, cellular distribution and localization of estrogen receptors (ERα and ERβ) in oesophageal adenocarcinoma in tissues from men and women.

Paraffin embedded oesophageal mucosal samples were obtained from 53 patients with oesophageal adenocarcinoma. Tissues were stained for ERα and ERβ using peroxidase-based immunohistochemistry and staining was visualised with brightfield microscopy. Cancer tissues were scored separately for ERα and ERβ. ERα and ERβ were detected in oesophageal adenocarcinoma tissues and were present in the cytoplasm and the nucleus. ERα showed more nuclear expression compared to ERβ, whereas ERβ showed more cytoplasmic expression. 39 (73.6%) patients with cancer had low nuclear expression of ERβ vs. 14 (26.4%) patients with high expression. The nuclear expression of ERβ was significantly higher in females than in males (P =0.0343). Given the known anti-oncogenic role of nuclear localised ERβ, these findings might indicate biological inactivity for ERβ in the majority of males with oesophageal adenocarcinoma.

Clinicopathological data were also collected and included: age, tumor location, treatment, TNM stage and survival. Higher expression of ERα was significantly associated with the presence of lymph node metastasis (P<0.05). A poorer response to radio- chemotherapy was significantly associated with higher expression of ERα (P<0.05), and distant metastases were more likely in men with higher expression of ERα.

This study identified significant gender-linked differences in expression and localisation of ERα/ERβ in oesophageal adenocarcinoma, and showed correlations between various clinical parameters and ER expression levels. This supports further exploration of estrogen signaling in the development of oesophageal adenocarcinoma.