title: Clinical evaluation of autoantibodies to p53 protein in patients with chronic liver disease and hepatocellular carcinoma.
abstract: In hepatocellular carcinoma (HCC) of patients from the Western hemisphere, mutations in the p53 tumour suppressor gene are present in up to 37% of cases. Conformational change and cellular accumulation can initiate an immune response with generation of circulating autoantibodies to p53 protein. In the present study, we investigated 711 consecutive patients with chronic liver disease to evaluate the sensitivity and specificity of autoantibodies to p53 protein as a serological marker for HCC. Detection of p53 autoantibodies was performed using an enzyme-linked immunosorbent assay with immobilised recombinant p53 protein. Liver cirrhosis was present in 259 patients (36.4%) and a HCC was diagnosed in 75 patients (10.6%). Autoantibodies to p53 protein were detectable in 15 of 377 patients with chronic liver disease (4.0%) and in 10 of 259 patients presenting with liver cirrhosis (3.9%). All 25 p53 autoantibody-positive/HCC-negative patients were carefully investigated and no underlying malignancy was clinically detected, suggesting that elevated p53 antibody levels may not exclusively be detectable in patients with malignant disease. In patients with clinically manifest HCC, p53 autoantibodies were detected in 17 of 75 cases, thus resulting in a sensitivity of 22.7% and a specificity of 96.1%. In contrast, assessment of serum alpha-fetoprotein (AFP) resulted in a sensitivity and specificity of 69.3 and 91.8% (AFP > 20 ng/ml) and 53.3 and 99.1% (AFP > 100 ng/ml) for the detection of HCC, respectively. The data of the present study reveal that the presence of p53 autoantibodies in patients with chronic liver disease is not completely specific for HCC. Moreover, we obtained no direct evidence that p53 autoantibody formation precedes the clinical diagnosis of HCC. However, serological screening for HCC might be improved by combining AFP and p53 autoantibody assays.
authors.affiliation: Second Department of Internal Medicine, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Raedle
authors.forename: G
authors.initials: G
authors.lastname: Oremek
authors.forename: M
authors.initials: M
authors.lastname: Truschnowitsch
authors.forename: M
authors.initials: M
authors.lastname: Lorenz
authors.forename: W K
authors.initials: WK
authors.lastname: Roth
authors.forename: W F
authors.initials: WF
authors.lastname: Caspary
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D001323:Autoantibodies; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins