P53 PROTEIN ACCUMULATION IN EUROPEAN HEPATOCELLULAR-CARCINOMA IS NOT ALWAYS DEPENDENT ON P53 GENE MUTATION

Background/Aims: Immunohistochemical reactivity for p53 protein is; co mmon in various human malignancies and often related to p53 gene mutat ion. However, in some tumor types, accumulation of wild-type p53 has b een shown. previously, we analyzed 96 European hepatocellular carcinom as using immunohistochemistry and found that 31% of these tumors overe xpressed p53 in the cell nucleus. the aim of the present study was to establish whether p53 positivity correlates with the presence of struc tural p53 gene abnormalities in European hepatocellular carcinoma. Met hods: DNA from 20 tumors, 10 with strong immunostaining and 10 with un detectable staining for p53, was extracted from frozen sections, and t he entire coding portion of the p53 gene was sequenced. Results: Five of the 10 tumors containing high levels of p53 protein showed missense point mutations. The remaining 5 tumors with high p53 levels showed t he wild-type coding sequence. One of the 10 tumors containing undetect able levels of p53 protein had a 1-base pair deletion in the splice ac ceptor site of intron 4. Conclusions: The results strongly suggest tha t, in European hepatocellular carcinomas, stabilization of the p53 pro tein depends on factors other than p53 gene mutation, such as binding to other molecules of cellular or viral origin.