Relevance of serum estradiol and estrogen receptor beta expression from a high-incidence area for esophageal squamous cell carcinoma in China

The striking 3-4:1 male predominance of esophageal squamous cell carcinoma (ESCC) has not yet been well explained. Our hypothesis is that the changes in level of estrogen and/or subtype of estrogen receptor (ER) may exert a protective factor in esophageal carcinogenesis and prognosis of ESCC. Radioimmunoassay (RIA) was used to determine the serum level of estradiol in healthy cohort from high-incidence area (HIA) and low-incidence area (LIA) for esophageal cancer as well as patients with ESCC from HIA in Henan, northern China. The ERβ expression profiling during the multi-stage progression of ESCC pathogenesis was evaluated by immunohistochemistry (IHC). Both males and females from HIA had significant decreases of serum estradiol in high-risk subjects predisposing for ESCC compared to healthy counterparts from LIA (P < 0.01). Furthermore, patients with ESCC from HIA developed the lowest level of estradiol (P < 0.01). ERβ expressed in precursor lesions of ESCC and changed quantitatively and qualitatively with disease progression during the multi-stages process of esophageal carcinogenesis. High frequency of ERβ expression was correlated with less aggressive potential of clinical behavior (P = 0.012, 0.015 for lymph node metastasis and tumor stage, respectively). This study indicates that lower serum level of estradiol may represent higher predisposition for development of ESCC, and ERβ expression and/or nuclear location may predict better outcome for patients with ESCC. The present results provide clues to explain the striking gender difference for ESCC, which warrants further investigations on potential applications of estrogen or analogs in prevention of ESCC.