Osteoponstin expression and presence of EGFR-positive liver macrophage to predict outcome after liver transplantation for hepatocellular carcinoma.
e15664 Background: Orthotopic liver transplantation (OLT) is the most effective therapy for patients with hepatocellular carcinoma (HCC) of limited extent. We focused on biomarkers, which could serve as tools for patient selection for OLT with good outcome even when transplanted beyond the standard size limits. Methods: Osteopontin(OPN) expression and presence of Epidermal Growth Factor Receptor (EGFR)-positive liver macrophage had been shown previously to be associated with the risk of tumor recurrence post OLT and were investigated immunohistochemically in 125 HCC-patients undergoing OLT between 1982 and 2002. Multivariate analyses of these and other well-described factors associated with median overall survival (OS) and time to recurrence (TTR) were performed. Results: The OS rates of the 125 patients at 1, 3, 5, 7 and 10 years were 77%, 52%, 43%, 37% and 32%. The 3-, 5-, and 7-year survival rates for patients without expression of both biomarkers (OPN and EGFR-positive liver macrophage) were 66.1%, 61.0% and 54.1%. These were significantly better than for the other groups (p < .0001), whereas the 3- and 7-year survival rates for patients with expression of both biomarkers were 25.0% and 5.0%. Fifty-eight patients (38.4%) developed tumor recurrence.There was no significant difference in OS and TTR between the patients beyond the Milan criteria (MC) without expression of both biomarkers (n = 26) and the patients within MC with expression of one or two biomarkers (n = 20).On multivariate analysis, vascular invasion and presence of EGFR-positive liver macrophage in HCC were independent factors associated with OS. Both biomarkers were independent factors associated with TTR.On multivariate analysis, morphologic criteria including MC and Up-to-7 criteria were not significantly associated with OS and TTR once OPN and EGRF+ macrophage presence was introduced into the analysis. Conclusions: Staining for OPN and EGFR-positive liver macrophage in HCC can give important prognostic information. The discussion about the selection for OLT in HCC patients should likely consider the expression of biomarkers in addition to relying on morphologic criteria.