DNA ploidy in hepatic cirrhosis, dysplasia and carcinoma: Evidence of clonal progression

Hepatocellular carcinoma (HCC) is the most common and aggressive form of primary liver tumors. The evolution and the putative association of this neoplasm with hepatic cirrhosis and liver cell dysplasia remain uncertain. We analyzed the DNA ploidy by flow cytometry in a cohort of 130 liver specimens representing liver cirrhosis, hepatic cell dysplasia and hepatocellular carcinoma to determine the incidence and potential biological relevance of this feature. Our results show that four (8.0%) of the 50 cirrhotic lesions, four (26.7%) of 15 dysplastic, and 51 (78.5%) of the 65 HCC manifested DNA aneuploidy. Moreover, DNA aneuploidy was manifested in 60% of histologically negative hepatic resection margins of HCC. Our results indicate that: i) the presence of DNA aneuploidy in some cirrhotic livers and liver cell dysplasias support the potential evolution of HCC from a subset of these lesions that harbor such clonal alterations, ii) DNA aneuploidy in histologically negative resection margins of HCC in some cases support the concept of field cancerization in these tumors and iii) the predominance of DNA aneuploidy and high proliferative index (PI) in liver cell carcinomas underscore their aggressive biological behavior.