Asynchronous DNA replication and aneuploidy in lymphocytes of hepatocellular carcinoma patients

Using fluorescence in situ hybridization (FISH) analysis, we examined the replication mode of the centromere region (homologous counterpart) and the aneuploidy level of chromosome 17 in the interphase nuclei of phytohaemagglutinin (PHA)–stimulated peripheral blood lymphocytes from (1) patients with hepatocellular carcinoma (HCC); (2) patients with liver cirrhosis (LC) due to hepatitis C viral infection who are individuals at a higher increased risk for HCC; and (3) healthy control participants. We also compared the allelic–replication asynchrony and aneuploidy frequencies with serum alpha-fetoprotein (AFP) levels. We found a significant increase in centromeric replication asynchrony accompanied by a high frequency of aneuploidy in lymphocytes of HCC patients compared with those of LC patients and healthy control participants. These changes are similar to those previously observed in other types of malignancy (hematological, ovarian, prostate, and breast cancer). The cytogenetic alterations of aneuploidy and strong asynchronous replication displayed in the lymphocytes of HCC patients arose from malignancy, as they were associated neither with an increased risk for cancer nor with an infection. The cytogenetic cancer-associated markers observed in patients' lymphocytes appeared to be superior to serum AFP, the marker currently used for HCC. Thus, the cytogenetic cancer-associated markers may be potentially useful in noninvasive cancer detection.