Differentiation of multicentric origin from intra-organ metastatic spread of hepatocellular carcinomas by comparative genomic hybridization

In hepatocellular carcinoma (HCC), multifocal growth may be due to intrahepatic metastatic spread or to the multicentric origin of clonal neoplasms. Although this issue is of potential clinical and prognostic importance, reliable differentiation cannot be achieved using clinical or morphological criteria alone. In this study, comparative genomic hybridization (CGH) was used to differentiate between metastatic spread and multicentric growth in two cases of HCC. In the first case, six carcinoma nodules were examined. The affected chromosomes and their pattern of aberrations were almost identical for all six nodules. In addition to aberrations of chromosomes 1, 4, 9, and 13, further aberrations were observed for chromosomes 2, 5, 7, and 17, which are less typical for HCC. These findings were seen as indicative of metastatic spread of the HCC. In the second case, 75% (3/4) of the nodules showed comparable aberration patterns involving chromosomes 1, 4, 8, 13, and 17, together with a number of further aberrations also not frequently seen in HCC including chromosomes 5, 7, 10, 12, 14, and 18. Chromosomes 4, 5, 8, 10, and 12 were also altered in the fourth nodule examined for this case, but they exhibited a unique aberration pattern. Additionally, gain of chromosome 15q was seen in only this fourth nodule. In the two cases examined, metastatic spread and multicentric origin of HCC could be differentiated by different patterns of karyotypic change. The CGH results were confirmed by fluorescence in situ hybridization (FISH). In conclusion, CGH facilitates the differentiation of multicentric growth from metastatic spread in HCC and appears to be superior to techniques previously used to resolve this clinically important diagnostic problem.