Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin

Field cancerization currently described the theory of tumorigenesis and, until now, has been described in almost all organ systems except in liver. For this reason, we explore the presence of field cancerization in liver and its underlying clinical implication in hepatocellular carcinoma (HCC). In our study, methylation profile of HCC and surgically resected margin (SRM) were established by methylation-specific PCR. Liver cirrhosis (LC), chronic hepatitis and normal liver were treated in the same way as the background control. The correlation analysis among the methylation profile of HCC, SRM and clinicopathological data of HCC patients was made respectively. Our results showed that methylation abnormities related to HCC, but not background disease existed in histologically negative SRM. Monoclonal and polyclonal models may coexist in field cancerization in liver. Patients with RIZ1 methylation in SRM had a shorter disease free survival. The local recurrence trend of early and later recurrence in HCC is potentially related to a second field tumor. From these results, we can suggest that field cancerization exists in liver. The study of field cancerization in liver plays an important role in hepatocarcinogenesis. Second field tumor derived form field cancerization may have important implications in HCC prognosis assessment that is worthy of further study. (Cancer Sci 2009; 100: 996-1004).