Loss at long arm of chromosome 4 as a predictive factor for recurrence of human hepatocellular carcinoma after orthotopic living-donor liver transplantation.

Abstract

e15054 Background: Living-donor liver transplantation (LDLT) is one of the curative treatments of hepatocellular carcinoma (HCC) that confined to the liver. To extend the indication of LDLT where candidate donors are more likely to be found than in liver transplantation from brain death, the Kyoto criteria (maximum tumor diameter < 5 cm, number of tumor < 10 nodules, serum PIVKA-II < 400 mAU/ml) has been proposed in addition to Millan criteria (< 5 cm for solitary nodule, or < 3 cm and < 3 nodules). The aim of this study was to identify genetic or epigenetic changes that predict recurrence in this setting. Methods: With informed consent, tumor and non-tumor tissues were obtained from 51 patients with HCC at the time of LDLT surgery. DNA copy number alterations were determined by microsatellite analysis and single nucleotide polymorphism array analysis. Mutational analyses for TP53 and CTNNB1 were performed by direct sequencing. DNA methylation status of 18 tumors was further analyzed using BeadChip Human Methylation 450. Results: Identified factors that indicate high risk for recurrence were: exceeding the Millan criteria (p = 0.0245, Log-rank test), exceeding the Kyoto criteria (p = 0.0007), hepatitis B virus infection (p = 0.0057), poorly differentiated tumor (p = 0.0245), loss of 4q34.3 (p = 0.0003), 14q (p = 0.0003), 17p (p = 0.0103), and gain of 8q24 (p = 0.0101), and high fractional allelic loss index (p < 0.0001). In patients who exceeded the Kyoto criteria for LDLT loss of 4q were associated with recurrences (5 recurrences for 6 cases with loss of 4q vs. no recurrence for 6 cases with retaining 4q). Conclusions: Genetic and epigenetic analysis combined with clinico-pathological features may help extending the indication for LDLT in patients with HCC.