Apoptosis and proliferation in relation to histopathological variables andprognosis in hepatocellular carcinoma

The prognosis of patients with resectable hepatocellular carcinoma depends mainly on the anatomical extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may b e of prognostic significance in hepatocellular carcinomas and that paramete rs of cell loss (usually, but not exclusively, due to programmed cell death ) are biologically relevant, the identification and quantitation of prolife rative capacity and apoptosis may be of prognostic importance. In this stud y four different methods have been used to assess proliferation in a series of 193 curatively (RO) resected hepatocellular carcinomas: mitotic count, immunohistochemical assessment of MIB-1 (Ki-67), proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNORs). A poptosis was assessed using the in situ-end labelling (ISEL) technique in c ombination with morphological criteria. Patients who received liver transpl antation were excluded. The results obtained were compared with histopathol ogical stage (according to UICC), Edmondson grade, several other histopatho logical factors, and survival rate. Significant statistical correlations we re seen between the mitotic index, the rate of nuclear positivity for MIB-1 and PCNA, and the number of AgNOR dots. In univariate survival analysis, t umour stage and Edmondson grade, mitotic index, MIB-1 and PCNA index, and m ean AgNOR number were significant factors influencing patients' survival. O n multivariate Cox survival analysis, mitotix index, concomitant cirrhosis, Edmondson grade, and patient age were the only significant independent pro gnostic factors. Apoptosis was not related to prognosis or to other paramet ers examined. These results indicated that mitotic index is an additional p rognostic parameter which could provide auxiliary information for patients' outcome. MIB-1 and PCNA immunostaining and AgNORs showed a good correlatio n among themselves. Apoptosis did not predict prognosis in hepatocellular c arcinoma. Copyright (C) 1999 John Wiley & Sons, Ltd.