The Clinical Study The Protective Mechanisms Of Estrogen In Hepatocellular Carcinoma

ObjectiveThe incidence of hepatocellular carcinoma (HCC) is prevalent in men compared to women. There was a study which reported the molecular mechanism of the gender disparity in HCC probably was the estrogen inhibiting the interleukin-6 (IL-6) production in animal model. However, the truly molecular mechanism of gender disparity in human HCC is uncertain. Here, we investigate the expression and clinical significance of Estrogen Receptorα(ERα) and Phosphorylated-ERα(p-ERα) in HCC, and the relationship between ERαexpression and prognostic in HCC patients. Furthermore, tentatively to study the association between ERα, p-ERαand IL-6.1.To investigate the correlation between ERαexpression and the biological characteristics of HCC (tumor size, number of nodules, with or without microscopic satellite lesions, with or without vascular invasion, with or without envelope), and analyse the effect of ERαto hepatocellular carcinoma patients prognosis.2. The aim of this study was to observe the expression levels and the correlation of ERα, phosphorylated-ERαand IL-6 between male and female patients with HCC tumor samples; Methods1. Selecting the age paired 77 (55 male and 22 female) specimens, underground radical liver resection hepatocellular carcinoma patients, Formalin-fixed, paraffin embedded sections was cut consectively into 3μm section to be placed on slides to detect the expression of three key molecules by immunohistochemistry method.2. Collecting fresh tumor specimens from hepatocellular carcinoma patients with radical liver resection normal liver tissue in patients with liver cancer, using Western blot, RT-PCR method to detect the molecular biological point of view to verify the pre-task inference.Results1. The positive rates of ERα, p-ERαand IL-6 in hepatocellular carcinoma were 39%(30/77), 45%(35/77) and 73%(56/77), respectively. The positive rate of ERαin patients with tumor size≤5 cm, serum level of AFP low 400 ng/ml, complete encapsulation and no-microvascular invasion was lower than those with tumor size>5 cm, serum level of AFP high 400 ng/ml, no-complete encapsulation and microvascular invasion (P<0.05). The overall survival rates of ERα-positive and ERα-negative patients were 66.7% and 23.4%(P<0.01). And the disease-free survival rates of ERα-positive and ERα-negative patients were 83.3% and 57.4%(P<0.05).2. The results of RT-PCR and western-blot showed that the mRNA level of ERαand p- ERαin normal tissue and the corresponding adjacent liver tissue were higher than in tumor tissues. Conversely, the mRNA and protein level of IL-6 in tumor tissues and the corresponding adjacent liver tissue were higher than in normal tissue.the results of immunhistochemistry showd: The ERαand p-ERαwere negatively correlated with IL-6 (r=-0.468, P<0.01; r=-0.370, P<0.01, respectively). Conclusion1. The tumor biological feature of ERα-postive patients is better than ERα-negative patients; the estrogen binding ERαmay be have protective role to hepatocellular carcinoma.2. The role of ERαin HCC may be related to IL-6 production in HCC.