Abstract
Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There have been several studies concerning ER expression in esophageal cancers, yet the results are inconsistent, and the prognostic value of the receptors remains unclear. In the present study, we investigated the expression of ER protein and its correlation with clinical features of esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining for the ERs was carried out on paraffin-embedded primary tumor tissue sections from 89 patients with ESCC. Quantitative analyses were performed to determine the prognostic value of the expression of ERs, and Pearson's correlation was used to examine the relationship between ERα and ERβ expression levels. Our results showed that ERα immunoreactivity was significantly lower in ESCC than that in the non-neoplastic epithelium (P=0.0445), whereas the ERβ status was much stronger in ESCC than that in the non-neoplastic epithelium (P=0.0243). A significant inverse correlation was observed between ERα expression and depth of tumor invasion (P=0.0426). Correlation analysis revealed a statistically significant inverse correlation between the expression of ERα and ERβ in ESCC (r=-0.2902, P=0.0058). Kaplan-Meier survival analysis showed that the patients with ERα expression (21/89) had a better outcome than patients without ERα expression (P=0.0280), whereas patients with high ERβ immunoreactivity (44/89) were significantly associated with worse survival (P=0.0366). In conclusion, ERα and ERβ levels were inversely correlated, and the downregulation of ERα and upregulation of ERβ may indicate unfavorable prognosis of ESCC.
Highlights
Human esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies
A significantly lower level of ERα immunoreactivity was detected in ESCC tissues than that in the normal esophageal tissues, which was consistent with the finding of Zuguchi et al [18]
The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues, and high expression of EZH2 was correlated with tumor aggressiveness and adverse patient outcome in ESCC [25,26]
Summary
Human esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. The prognosis of ESCC female patients is significantly better than that of male patients [2]. While these data indicate the potential involvement of sex hormone-related pathways in the pathogenesis of ESCC, the relevant molecular events remain unclear. Esophageal cancer in females tends to occur postmenopausally, and the incidence rate for females increases with age [5]. Sex steroids, such as estrogen, are well-known for their role(s) in the control of cell differentiation and proliferation in estrogen-dependent tissues such as breast and endometrial tissues. Estrogenic pathways may be involved in the regulation of the biological behavior of ESCC
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