Correlation between tumor clonal origin of pluri-nodular hepatocellular carcinoma and recurrence of tumor after liver transplantation

Abstract

Objective To investigate the correlation between the clonal origin of hepatocellular carcinoma (HCC) and the recurrence of pluri-nodular HCC after liver transplantation. Methods Sixty pluri-nodular HCC patients, conformed to the UCSF's standard, were selected and given liver transplantation. Then tumor nodules were separated from the normal tissue by microdissection. The state of 12 HCC high frequency microsatellite loss of heterozygosity (LOH) was detected by SSCP-PCR, and the tumor clone origin for intrahepatic metastasis (IM), multicentric occurrence (MO) and IM+ MO type was determined. The correlation between different types of clonal origin and the three-year tumor-free survival rate, tumor pathological features and the level of serum AFP was analyzed. Results Forty-five cases had two nodules of HCC, and the rest 15 cases had three nodules. After excluding two cases whom the clonal origin pattern was not identified, the remaining 58 cases were enrolled in the study. The IM group, MO group and IM+ MO group were set up, accounting for 34.48% (20/58), 56.90% (33/58) and 8.62% (5/58) respectively. In IM group, MO group and IM+ MO group, the three-year tumor-free survival rate was 50.00%, 78.79% and 40%; the incidence of MVI was 100%, 18.18% and 100%; the low differentiation rate of tumor was 80%, 51.52% and 80%; and the mean concentrations of AFP were 231.25 (2.78-9736.27), 24.59 (1.16-2674.50) and 122.58 μg/L (16.20-1608.03 μg/L) respectively. Conclusion The three-year tumor-free survival rate of MO was significantly higher than that of IM and IM+ MO types, which was closely related to the low incidence of tumor thrombi, the high degree of pathological differentiation and low preoperative AFP. Tumor clonal origin may serve as an important reference index for the evaluation of the disease stage of multiple nodules HCC and predict the risk of tumor recurrence after liver transplantation. Key words: pluri-nodular hepatocellular carcinoma; clonal origin; loss of heterozygosity; liver transplantation; pathology; tumor recurrence