HEPATOCELLULAR CARCINOMAS WITH A HIGH PROLIFERATION INDEX AND A LOW DEGREE OF APOPTOSIS AND NECROSIS ARE ASSOCIATED WITH A SHORTENED SURVIVAL

In this study we investigated tumour growth in relation to the immunoh istochemical expression of p53 and bcl-2 and to patient survival data in 33 operated hepatocellular carcinomas (HCCs). In order to estimate the growth, a growth index, based on the degree of cell proliferation, apoptosis and necrosis, was calculated for each tumour. Cell prolifer ation was determined immunohistochemically by the number of proliferat ing cell nuclear antigen (PCNA)-positive cells in tumours, the extent of apoptosis was determined by counting the number of cells labelled b y the in situ 3'-end labelling technique and tumour necrosis was estim ated as the percentage of necrotic areas in haematoxylin-eosin-stained tissue sections. In our analysis we found that the survival of patien ts with HCCs showing a high growth index (i.e. tumours showing a high proliferation and simultaneously a low degree of apoptosis and necrosi s) was significantly shorter than with other patients (P = 0.004, log- rank test). When analysed separately, cell proliferation, apoptosis or necrosis did nor show any significant association with survival. p53 positivity was found in 8/33 (24%) of tumours. There were significantl y more p53-positive cases in tumours with a high growth index (P=0.01, Fisher's exact test) suggesting that dysfunction of the p53 gene may affect tumour growth. p53-positive cases did not, however, have a sign ificantly shorter survival time than p53-negative casts (P=0.3, log-ra nk test). bcl-2 positivity was found in only 1/33 (3%) of the HCCs. Th us bcl-2 overexpression does not seem to play an important role in hep atocellular carcinogenesis. In summary, our results suggest that in HC Cs a compound score based on the evaluation of the degree of cell prol iferation, apoptosis and necrosis is a biologically more relevant prog nostic indicator than any of its composite parameters alone.