DNA topoisomerase IIα and Ki67 are prognostic factors in patients with hepatocellular carcinoma

Abstract

The present study was designed to determine the significance of DNA topoisomerase IIa (TopoIIα) and Ki67 in hepatocellular carcinoma cells (HCCs). The present study included 353 patients with HCC. The association of clinicopathological data with the expression of TopoIIα and Ki67 by immunohistochemistry was analyzed by χ² test. Cox multivariate proportional hazards regression analysis and Kaplan-Meier analysis were performed with all the variables to derive risk estimates associated with overall survival (OS)/recurrence-free survival (RFS) and to control for confounders. TopoIIα and Ki67 were detected in the nuclei of the tumor cells. With TopoIIα, 35.7% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. With Ki67, 37.1% of cells exhibited high expression, which was associated with tumor-node-metastasis stage, tumor size and α-fetoprotein level. Correlation was identified between the expression level of TopoIIα and Ki67 in HCCs (r=0.444). Multivariate analysis revealed that high TopoIIα expression is a prognostic indicator for RFS [hazard ratio (HR), 2.002; 95% confidence interval (CI), 1.429-2.806] and OS (HR, 2.749; 95% CI, 1.919-3.939), and high Ki67 expression is a prognostic indicator for OS (HR, 1.816; 95% CI, 1.273-2.589). The TopoIIα-low group had a significantly increased RFS rate (55.6 vs. 31.7%) and OS rate (66.5 vs. 23.8%) compared with the TopoIIα-high group. The OS rate was increased in the Ki67-low group compared with the Ki67-high group (67.0 vs. 26.5%). Expression of TopoIIα and Ki67 are independent prognostic factors for survival in HCCs. TopoIIα was positively associated with Ki67 expression.

Keywords: DNA topoisomerase IIα; Ki67; hepatocellular carcinoma; prognosis.

Figure 1.

Observation of nuclear Ki67 staining in a case of HCC. (A) High expression of Ki67 in HCC (magnification, ×200). (B) High expression of Ki67 in HCC (magnification, ×400). Observation of nuclear TopoIIα staining in a case of HCC. (C) High expression of TopoIIα in HCC (magnification, ×200). (D) High expression of TopoIIα in HCC (magnification, ×400). HCC, hepatocellular carcinoma; TopoIIα, topoisomerase IIα.

Figure 2.

Kaplan-Meier survival curves demonstrating (A) decreased overall survival and (B) recurrence-free survival in the TopoIIα-high group, and (C) decreased overall survival in the Ki67-high group. TopoIIα, topoisomerase IIα.