FLOW CYTOMETRIC DNA ANALYSIS OF CIRRHOTIC LIVER-CELLS IN PATIENTS WITH HEPATOCELLULAR-CARCINOMA CAN PROVIDE A NEW PROGNOSTIC FACTOR

BACKGROUND. DNA flow cytometry of hepatocellular carcinoma (HCC) cells has been investigated in many studies, but, to the best of our knowle dge, there are no data on DNA analysis of cirrhotic parenchyma around the HCC. In this study, cell kinetics and ploidy of parenchymal cells around HCC were performed to ascertain if this would predict the possi bility of recurrence in the cirrhotic areas. METHODS. The DNA content of 93 cases of HCC and of cirrhotic liver around the tumor nodules was analyzed by flow cytometry. Ploidy and proliferative index of HCC and cirrhotic liver were compared with macroscopic, histologic, and clini cal features of each case and linked with the behavior of these tumors . Survival curves were assessed according to the Kaplan-Meier method. A multivariate analysis based on Cox proportional hazards regression m odel was performed on cases of diploid cirrhosis cells in which the S- phase fraction was evaluable. RESULTS. The univariate analysis of surv ival suggested significant roles for age, number of intrahepatic nodul es, Edmondson-Steiner's classification, portal invasion, vascular inva sion, presence of necrosis, hepatitis B surface antigen, alpha-feto-pr otein, Child's score, ploidy, and S-phase fraction of HCC cells. The D NA analysis of the cirrhotic cells showed that polyploidy was dramatic ally reduced in patients with HCC, compared with normal hepatocytes, a nd aneuploid clones were present among diploid cells. High S-phase fra ction of cirrhotic cells and Child-Pugh classification were the strong est independent parameters affecting the tumor behavior in this study. CONCLUSIONS. The results of this study suggest that S-phase fraction of cirrhotic liver parenchyma may be employed as a new parameter in th e prognostic evaluation of HCC patients. (C) 1996 American Cancer Soci ety.