Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria

Background & Aims: Microarray data showed that osteopontin overexpression predicts early HCC-recurrence after liver resection. Osteopontin (OPN) expression could serve as a predictor of HCC-recurrence after OLT. Methods: Osteopontin expression was investigated immunohistochemically in a unique population of 125 HCC-patients undergoing OLT between 1982 and 2002, including 81 patients (65%) outside the Milan criteria. Multivariate analysis of factors associated with median overall survival (OS) and time to recurrence (TM) was performed. Results: Osteopontin was expressed in 40/125 (32%) of the HCCs. Overall survival post-OLT at 1, 2, 3, 5 years was 77%, 62%, 52%, and 43% (median survival 37 months). Overall survival was significantly longer without expression of OPN (p<0.05; (median OS: 56 vs. 23 months). The same was true for median TTR (p = 0.008). Outside Milan criteria, patients without OPN-expression had better prognosis (median OS: 37.8 vs. 19.2 months, p = 0.003). Tumor recurrence in patients transplanted outside Milan criteria occurred in 43% (23 of 54) of patients without and 70% (19 of 27, p = 0.018) of patients with OPN-expression after a median TTR of 83.5 vs. 13.9 months. On multivariate analysis, vascular invasion and OPN-expression were independently associated with OS and TTR in HCC-patients after OLT. Conclusions: Immunohistochemically detectable Osteopontin in HCC is an independent predictor of tumor recurrence and survival in patients beyond Milan criteria undergoing OLT. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.