Genetic difference between multicentric carcinogenesis and intrahepatic metastasis of multiple hepatocellular carcinoma.

Abstract

307 Background: Multiple hepatocellular carcinoma (HCC) is categorized into 2 types; multicentric carcinogeneis (MC) and intrahepatic metastasis (IM). Although discrimination of the types of multiple HCC is of clinical importance, it is difficult to determine it correctly even after histological diagnosis. Methods: In order to classify multiple HCC into MC and IM, we compared pairs of multiple HCC and matched non-tumoral liver samples from 22 patients who were clinically diagnosed MC and 8 patients with IM with regard to molecular aberrations using next generation sequencer. Results: Exome sequence showed that among the 22 patients with clinical MC, 7 patients were genetically determined as having IM (gIM) because of the concordance of mutations, while all the patients with clinical IM were as having MC (gMC). In 15 patients with gIM, 125 mutations (90.6%) per patient were common, which were consistent with the result of a pair of primary HCC, and only a few passenger mutations were different between IM specimens suggesting that IM pairs developed from the common ancestor. On the other hand, 138 somatic mutations per tumor, and no common somatic mutations were identified in the 15 patients with gMC. Clinically, vascular invasion was significantly frequent in gIM group ( P = 0.007). On the other hand, after a median follow-up of 2.56 years (range; 0.27−6.32 years), the median overall survivals were 3.7 years (95%CI, 1.26–6.14) and 3.37 years (2.02−6.32, P = 0.712) in the patients with IM and MC, respectively. The 3-year rates of overall survival were 71.7% and 65.1% in the two groups, respectively. Conclusions: Taken together, genetic comparison of mutations in a pair of HCCs makes it possible to classify MC and IM, which is available to make treatment plan for multiple HCC patients.