THE HUMORAL IMMUNE-RESPONSE TO P53 IN PATIENTS WITH HEPATOCELLULAR-CARCINOMA IS SPECIFIC FOR MALIGNANCY AND INDEPENDENT OF THE ALPHA-FETOPROTEIN STATUS

Recently, p53 gene aberrations have been recognized as a relevant fact or in hepatocarcinogenesis, in tumors from both high-risk and low-risk areas. Because p53 gene mutations typically result in increased p53 l evels in tumor cells, this cellular protein might become immunogenic d uring tumor development. To test this hypothesis, we have analyzed ser a from 80 European patients with hepatocellular carcinoma for the pres ence of p53 antibodies. For this purpose we developed an immunoblot as say using recombinant p53 as antigen. Sixty-seven sera from patients w ith different acute and chronic liver diseases were used as controls. In addition, serum alpha-fetoprotein assays were performed. Circulatin g antibodies against p53 were found in 25% (20 of 80) of the sera from patients with hepatocellular carcinoma but not in various nonmalignan t liver diseases. The association of p53 antibodies with malignancy wa s highly significant (p < 0.00003). In 73.8% (59 of 80) of the hepatoc ellular carcinoma sera the alpha-fetoprotein levels were elevated. Amo ng the 21 alpha-fetoprotein-negative hepatocellular carcinoma sera, 5 were found to contain p53 antibodies (23.8%). In conclusion, an antibo dy response against p53 developed in a significant proportion of patie nts with hepatocellular carcinoma but not in those with nonmalignant l iver diseases. Serological testing for p53 antibodies gives the opport unity to identify a subgroup of patients with hepatocellular carcinoma not detected by conventional tests for serum alpha-fetoprotein.