Tumor recurrence following liver transplantation for hepatocellular carcinoma: role of tumor proliferation status

The selection of patients with hepatocellular carcinoma for liver transplantation is currently based on the size and number of tumors to minimize the risk of recurrence. These criteria measure tumor bulk but may not reflect tumor behavior accurately. A biological marker of tumor behavior could aid with patient selection further. The aims of this study were to determine factors associated with a higher risk of tumor recurrence and to assess the role of tumor proliferation status with respect to recurrence following transplantation. Pathological data on 67 patients who underwent transplantation for hepatocellular carcinoma were reviewed, and tumor proliferation was assessed by minichromosome maintenance protein-2 (MCM-2) and cyclin A expression. A Cox regression analysis of factors related to tumor recurrence and overall survival was carried out. Recurrence-free survival was assessed according to compatibility with selection criteria, vascular invasion, and proliferation status. Tumor size, vascular invasion, and highest MCM-2 expression were associated with tumor recurrence by multivariate analysis (P < 0.02). Recurrence-free survival was significantly better for those patients without vascular invasion, those who were within the Milan, University of California San Francisco (UCSF), or Up-to-Seven selection criteria, and those with lower expression of MCM-2. In conclusion, tumors meeting the Milan, UCSF, or Up-to-Seven selection criteria had a lower rate of recurrence following liver transplantation. Vascular invasion and tumor proliferation status were associated with the risk of recurrence independently of tumor size. Biopsy of larger tumors to assess proliferative activity could identify those at lower risk of recurrence who could also benefit from liver transplantation.