Clonality analysis for multicentric origin and intrahepatic metastasis in recurrent and primary hepatocellular carcinoma

Aims To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus in China and to identify the differences between them. Methods Histopathologic and genetic features of primary and recurrent tumors in 160 cases with HCC were analyzed. The two groups, the origin of which was definitely determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their disease-free survival and clinicopathological differences. Results According to histopathological findings, 27.5% and 59.4% patients were considered to be MO and IM, respectively. By comparing the genetic information of loss of heterozygosity and microsatellite instability for 10 different markers between primary and recurrent tumor, 30.0% and 63.8% patients with recurrent HCC were considered to be MO and IM, respectively. In total, 126 cases with unanimous conclusions from the histopathological and genetic method were selected and divided into the MO group (37 cases) and the IM group (89 cases). Analysis of stepwise regression identified that recurrence time, grading, portal vein invasion, tumor number, and Child's stage were the most important discriminating factors between MO and IM (p < 0.05). As for their prognosis, Kaplan-Meier and log rank test showed that the disease-free survival in the MO group was significantly better than in the IM group (p=0.002). Conclusions Combined analysis of histopathological and genetic analysis may reflect more exactly the nature of recurrent HCC. The incidence of MO in China is lower than in other countries-30% compared to up to 50% in Japan [Morimoto et al., Journal of Hepatology 39:215-221, 2003; Yamamoto et al., Hepatology 29;1446-1452, 1999]. Recurrence time, tumor grading, portal vein invasion, tumor number, and Child's stage are the most important discriminating factors between MO and IM. The prognosis (disease-free survival) of patients with MO compared to IM is significantly better.