Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) in the diagnosis of hepatocellular carcinoma

Abstract.

Background: The histomorphological diagnosis of well differentiated hepatocellular carcinoma (HCC) may be a challenging task, because regenerative nodules and adenomas share similar microscopic features. Moreover, the differentiation of intrahepatic metastatic spread from multicentric growth in multinodular HCC is frequently not possible by histological criteria alone. Whether molecular cytogenetic analysis can contribute to the differential diagnosis of HCC was recently investigated by our group.

Methods: We applied comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) to 12 cases of hepatocellular adenoma (HCA) and 28 cases of well differentiated HCC.

Results: CGH revealed aberrations in 2/6 HCAs, affecting 7p in 1 sample each and 17q and 20 in the second case. In 4/4 well differentiated HCCs, aberrations occurred, with a mean of eight aberrations per case, focused on 1q, 4q, 8p, 8q, 16p, and 17p. In all HCC samples, at least two of these sites were affected. In 2 multinodular HCCs, six and four different tumor nodes, respectively, were analyzed. In the first case, aberration patterns of chromosomes 1, 4, 5, 9, 13, and 17 were almost identical in all six nodes, indicating metastatic spread. In the second case, three of the nodes showed very similar patterns of chromosome aberrations, including those of chromosomes 1, 4, 5, 7, 8, 10, 12, 14, 17, and 18. Aberrations of chromosomes 4, 5, 8, 10, 12, and 15 were shown in the fourth node, findings conclusive for both the metastatic spread and the multicentric origin of the HCC. Based on the CGH results, five probes, for chromosomes 1, 6, 7, 8, and X, were selected for FISH. Using this panel, we found no aberrations in 14 HCAs. By contrast, 13/14 HCCs demonstrated aberrations for two to five chromosomes in the FISH analysis.

Conclusions: We conclude that CGH and FISH are helpful diagnostic tools for the histopathological differential diagnosis of HCC.