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 (TTR) was performed.

Results

Osteopontin was expressed in 40/125 (32%) of the HCCs. Overall survival post-OLT at 1, 2, 3, 5years was 77%, 62%, 52%, and 43% (median survival 37months). Overall survival was significantly longer without expression of OPN (p<0.05; (median OS: 56 vs. 23months). 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. 19.2months, 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. 13.9months. 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.

Abbreviations: HCC, hepatocellular carcinoma, OLT, orthotopic liver transplantation, OPN, osteopontin, TACE, transarterial chemoembolization, RFA, radiofrequency ablation, PEI, percutaneous ethanol injection, HR, hazard ratio, TTR, time to recurrence

Keywords: Osteopontin, Hepatocellular carcinoma, Recurrence, Survival, Liver transplantation