Ki-67 and DNA topoisomerase IIα predict survival in patients with primary hepatocellular carcinoma after liver transplantation

Abstract

Objective To investigate whether Ki-67 and DNA topoisomerase Ⅱα (TopoⅡα) are effective prognostic markers in patients with primary hepatocellular carcinoma (HCC) after liver transplantation. Methods This retrospective cohort study included 105 patients with HCC who underwent liver transplantation in a single center from 2001 to 2012. The demographic features, clinicopathological data, expressions of TopoⅡα and Ki-67 as detected by immunohistochemistry. The long-term survival and the potential prognostic factors, together with standard histologic parameters, were analyzed by univariate and multivariate analyses. Results A positive correlation was found between TopoⅡα and Ki-67 levels in HCC (r=0.469, P<0.01). Multivariate analyses showed that Ki-67 was an independent prognostic risk factor of recurrence-free survival (HR=2.296, P<0.05). The 5-year overall survival rate was related to tumor size (HR=1.743, P<0.05), AFP (HR=2.291, P<0.05), histological grade (HR=0.283, P<0.01), and high expressions of Ki-67 (HR=1.977, P<0.05) and TopoⅡα levels (HR=1.883, P<0.05). The Kaplan-Meier analysis showed that there was a significant difference in the 5-year recurrence-free survival rate (40.4% vs. 57.6%) between patients with high and low expressions of Ki-67, which were significantly lower in the high TopoⅡα expression patients (13.5% vs. 63.8%) (P<0.01). The 5-year overall survi-val rates were significantly lower in the high Ki-67 expression patients (12.7% vs. 61.1%, P<0.01) when compared with the low Ki-67 expression patients, which were significantly lower in the high TopoⅡα-and Ki-67 expression patients (10.7% vs. 54.5%, P<0.01) than the low TopoⅡα-or Ki-67 patients. Conclusions Ki-67 was associated with recurrence and metastasis in patients with primary hepatic carcinoma after liver transplantation. High expression of both Ki-67 and TopoⅡα were associated with poor prognosis in these patients. Key words: Hepatocellular carcinoma; Liver transplantation; Ki-67; DNA topoisomerase Ⅱα(TopoⅡα); Prognosis