Chromosomal Alterations in Hepatocellular Nodules by Comparative Genomic Hybridization: High-Grade Dysplastic Nodules Represent Early Stages of Hepatocellular Carcinoma

• Published in: Laboratory investigation Vol. 82; no. 5; pp. 547 - 553
• Main Authors: Tornillo, Luigi, Carafa, Vincenza, Sauter, Guido, Moch, Holger, Minola, Ernesto, Gambacorta, Marcello, Vecchione, Raffaela, Bianchi, Leonardo, Terracciano, Luigi M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2002; Nature Publishing; Nature Publishing Group
• Subjects: Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Chromosome Aberrations; DNA, Neoplasm - analysis; Female; Focal Nodular Hyperplasia - genetics; Focal Nodular Hyperplasia - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Image Processing, Computer-Assisted; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Nucleic Acid Hybridization; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Tumors; Chromosomal aberration; Human; Dysplasia; Pathogenesis; Liver; Hepatic disease; Hepatocellular carcinoma; Early stage; Malignant tumor; Carcinogenesis; Nodule; Regeneration; Digestive diseases; Genetics
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3780449

Data from experimental hepatocarcinogenesis and recent studies in humans have suggested that the emergence of hepatocellular carcinoma (HCC) is a stepwise process. However, despite abundant experimental data, the precise molecular mechanisms and genetic alterations involved in human liver carcinogenesis are still unclear. Comparative genomic hybridization was used to analyze 26 hepatocellular nodules obtained from patients undergoing liver transplantation or surgical resection for HCC. According to the criteria proposed by the International Working Party, 16 nodules were classified as multiacinar regenerative nodules (MRN), 4 as low-grade dysplastic nodules (LG-DN), and 6 as high-grade dysplastic nodules (HG-DN). Our aim was to investigate the possible genetic differences between MRN, LG-DN, and HG-DN. The whole group of nodules showed only a few aberrations (mean 1.1/case), without any significant pattern. This finding is comparable to what happens in non-neoplastic tissue. On the contrary, in three of six HG-DN, we found deletions of 8p and gains of 1q. LG-DN and MRN did not show these chromosomal imbalances. These results confirm the important role of allelic losses on 8p as well as of gains of 1q in HCC. We conclude that the genes that are important in early stages of hepatocarcinogenesis are probably located on these chromosomal arms.