Prognostic significance of proliferation markers in hepatocellular carcinoma (HCC)

BACKGROUND: The prognosis of patients with curatively resectable hepatocellular carcinoma depends mainly on anatomic extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may be of prognostic significance in hepatocellular carcinomas, identification and quantitation of proliferative capacity may be of prognostic importance. METHODS: We have compared four different methods to assess proliferation in a series of 193 curatively (R0-) resected hepatocellular carcinomas: Mitotic count, immunohistochemical assessment of the MIB-1- (Ki-67-), Antigen Proliferating Cell Nuclear Antigen (PCNA) and silverstained nucleolar organiser regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), Edmondson Grade and with survival rate. RESULTS: In each carcinoma, we could demonstrate mitotic figures, MIB-1, PCNA and AgNOR dots in variable proportions. Significant statistical correlations were seen between Mitotic Index, the rate of nuclear positivity for MIB-1 and PCNA and the number of AgNOR dots. In univariate survival analysis tumour stage and Edmondson Grade, Mitotic Index, MIB-1 and PCNA Index and mean AgNOR-number were significant patients' survival influencing factors. Performing multivariate Cox survival analysis, Mitotic Index, concomitant cirrhosis, Edmondson Grade and patient age were the only significant independent prognostic factors. CONCLUSION: These results indicated that Mitotic Index is an additional prognostic parameter which could provide auxiliary information for patients' outcome.