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 intrahep atic metastatic spread or to the multicentric origin of clonal neoplasms. A lthough this issue is of potential clinical and prognostic importance, reli able differentiation cannot be achieved using clinical or morphological cri teria 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 a ffected chromosomes and their pattern of aberrations were almost identical for all sis nodules, In addition to aberrations of chromosomes 1,4, 9, and 13, further aberrations were observed for chromosomes 2, 5, 7, and 17, whic h are less typical for WCC. These findings were seen as indicative of metas tatic spread of the HCC. In the second cast, 75% (3/4) of the nodules showe d 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 chromoso me 15q was seen in only this fourth nodule. In the two cases examined, meta static spread and multicentric origin of HCC could be differentiated by dif ferent patterns of karyotypic change. The CGH results were confirmed by flu orescence in situ hybridization (FISH). In conclusion, CGH facilitates the differentiation of multicentric growth from metastatic spread in HCC and ap pears to be superior to techniques previously used to resolve this clinical ly important diagnostic problem. Copyright (C) 2000 John Wiley & Sons, Ltd.