Predictive Value Of Topoisomerase Ⅱ Alpha Protein For Clinicopathological Characteristics And Prognosis In Early Breast Cancer

Background:Topoisomerase II alpha(TOP2A)has been identified as a proliferation marker,of which the most common method for detection is immunohistochemistry(IHC).However,the optimal cut-off of TOP2A expression regarding prognostic value remains controversial.This study was to identify the optimal cut-off value of TOP2A expression and its correlation with clinicopathological variables and prognosis in early-stage breast cancer in China.Methods:Between January 2013 and January 2015,a total of 1084 early breast cancer patients were enrolled.The optimal cut-off of TOP2A expression was assessed using the minimum P value approach.Correlations between TOP2A expression and clinicopathological characteristics were explored by the Spearman’s correlation analysis,while the impact of TOP2A expression on disease free survival(DFS)and overall survival(OS)was evaluated by the Kaplan-Meier methods.Univariate and multivariate Cox regression analyses were executed to identify statistically significant prognostic factors.Results:The optimal cut-off value of TOP2A was recommended as 15%.Overall,603(5 5.6%)patients were TOP2A over-expression and 481(44.4%)patients were TOP2A lowexpression.TOP2A over-expression was in positive associations with a higher ki67 index(r=0.83,P<0.001),HER2 positive(r=0.24,P<0.001),a larger tumor size(r=0.15,P<0.001),and a higher histologic grade(r=0.59,P<0.001),and in a significantly negative correlation with hormone receptor(HR)positive expression(r=-0.40,P<0.001)in early breast cancer.TOP2A over-expression significantly associated with worse DFS(P=0.001)and OS(P<0.001)and was an independent prognostic factor for both DFS(hazard ratio[HR]=1.72;95%confidence interval[95%CI]:1.13-2.59,P=0.01)and OS(HR=3.54;95%CI:1.538.23,P=0.003)in stage Ⅰ-Ⅱ breast cancer patients.Conclusions:To our knowledge,this is the first study to recommend the optimal cut-off value of TOP2A expression in breast cancer.The TOP2A expression is significantly correlated with HER2 status,ki67 index,tumor size,histologic grade,and HR status,and could be a surrogate indicator for poor prognosis of early breast cancer.