Expression Of SOX4 And EZH2 In Breast Cancer Tissues And Their Clinicopathologic Significances

Background: Breast cancer is the most common malignant tumor of females worldwide.Patients suffering from breast cancer usually die from metastasis.Some researches indicated that both sex-determining region Y-related high mobility group box4(SOX4)and enhancer of zeste homolog 2(EZH2)could promote tumor metastasis by inducing epithelial-mesenchymal transition(EMT).But it is unclear that SOX4 and EZH2 have a correlation in breast cancer tissues.As an important supplementary means,immunohistochemistry can detect protein expression in tumor tissues simply,directly and specifically which not only can help tumor patients including breast cancer patients confirm diagnoses,but also can evaluate tumor prognosis to some extents and guide clinical therapy.Objective: To explore the expression of SOX4 and EZH2 in breast cancer tissues,and analyze their clinicopathologic significances and correlation.Methods: The expression of SOX4 and EZH2 was detected by immunohistochemistry in paraffin-embedded tissue sections from 241 cases of breast cancer and 126 cases of paracancerous breast tissues.Meanwhile we detected the expression of EMT markers,E-cadherin and vimentin,in 129 cases of breast cancer.After observing results under microscope,the relationship between the expression of SOX4/EZH2 and clinicopathologic characteristics was statistically analyzed.Meanwhile the correlation between the expression of SOX4 and EZH2 and the relationship between them and E-cadherin,vimentin was also analyzed.Results:1.The expression of SOX4 located in cytoplasm and/or in cell nucleus of mammary epithelial cells and cancer cells,and diffused across breast cancer nests.Compared with paracancerous breast tissues with 57.1%(72/126)high expression rates,SOX4 was upregulated in breast cancer tissues with 82.2%(198/241)high expression rates(P<0.05).2.The expression of EZH2 located in cell nucleus of mammary epithelial cells and cancer cells,and diffused across breast cancer nests.Compared with paracancerous breast tissues with 47.6%(60/126)high expression rates,EZH2 was upregulated in breast cancer tissues with 80.1%(193/241)high expression rates(P<0.05).3.High SOX4 expression was correlated with lymph node metastasis,TNM stages,and the high expression of HER-2(P<0.05).The expression of SOX4 increased with rising TNM stages(P<0.008).4.High EZH2 expression was correlated with histological grades,lymph node metastasis,ER negativity,EGFR positivity and the high poliferation index of Ki-67(P<0.05).Molecular subtypes of breast cancer were also associated with high EZH2expression(P<0.05),which high EZH2 expression of HER-2 overexpression type was higher than Luminal A type(P<0.008).5.The expression of E-cadherin located in cytomembrane of cancer cells,which was heterogeneous in cancer nests and atypical obviously cancer cells were always negative.50.4%(65/129)of cases lost E-cadherin expression.The expression of vimentin located in cytoplasm of cancer cells,which was heterogeneous in cancer nests and atypical obviously cancer cells were always positive.Its positive rate was73.6%(95/129).6.The expression of E-cadherin was negative correlated with the expression of vimentin(rs=-0.357,P<0.05);both SOX4 and EZH2 were negative correlated with the expression of E-cadherin(rs=-0.246,P<0.05;rs=-0.357,P<0.05),which were positive correlated with the expression of vimentin(rs=0.310,P<0.05;rs=0.268,P<0.05).7.There was a positive correlation between SOX4 and EZH2 expression in breast cancer tissues(rs=0.256,P<0.05).Conclusion: SOX4 and EZH2 might be responsible for the lymphatic metastasis of breast cancer via promoting EMT,which are upregulated in breast cancer tissues.They may act as potential biomarkers to predict the metastasis of breast cancer.