ANTI-P53 ANTIBODIES IN SERA OF WORKERS OCCUPATIONALLY EXPOSED TO VINYL-CHLORIDE

Background: The p53 tumor suppressor gene (also known as TP53) is ofte n mutated in a wide variety of cancers, including angiosarcoma of the liver (ASL). Anti-p53 antibodies have been detected in the sera of pat ients with leukemia, childhood lymphoma, or cancers such as those of t he breast, lung, colon, esophagus, and liver (hepatocellular carcinoma ). Purpose: The objective of this study was to determine the prevalenc e and time of appearance of serum anti-p53 antibodies during the patho genesis of ASL associated with occupational exposure to vinyl chloride . Methods: Enzyme-linked immunoassay (EIA) was used to detect anti-p53 antibodies in 148 serum samples from 92 individuals occupationally ex posed (in France or in Kentucky) to vinyl chloride; 15 of these indivi duals (six from France and nine from Kentucky) had ASL. A subset of co ded EIA-positive and EIA-negative sera was further analyzed for anti-p 53 antibodies by immunoblotting and immunoprecipitation. Nucleotide se quence analysis of exons 5-8 of the p53 gene was conducted on ASL DNA from six patients. We tested sera from 31 men who had no occupational exposure to vinyl chloride; they made up the control group. Statistica l analyses were done using the Kruskal-Wallis chi-squared approximatio n and the Wilcoxon two-sample test for normal approximation. All P val ues result from tyro-sided tests. Results: Fourteen serum samples (fro m nine individuals) mere positive in the EIA. Five of the 15 individua ls with ASL were positive for anti-p53 antibodies by EIA, immunoblotti ng, and immunoprecipitation: one individual at 11.3 and 10.8 years bef ore diagnosis, another at 4 months before and shortly after diagnosis, and three when diagnosed or shortly thereafter. Four of the 77 vinyl chloride-exposed workers without diagnosed ASL were positive for anti- p53 antibodies; two of the four had symptoms related to vinyl chloride toxicity. Tumors from three of the six vinyl chloride-exposed workers from which sufficient DNA for analysis was obtained had A:T to T:A mi ssense mutations of the p53 gene. Anti-p53 antibodies were detected in two of these individuals. Among the control group, two of 15 serum sa mples from 15 lung cancer patients and zero of 15 serum samples from c ontrol subjects without cancer had anti-p53 antibodies at substantiall y lower levels than the nine (10%) of 92 vinyl chloride-exposed worker s who were positive for anti-p53 antibodies. Conclusions and Implicati ons: Serum anti-p53 antibodies can predate clinical diagnosis of certa in tumors, such as ASL, and may be useful in identifying individuals a t high cancer risk, such as workers with occupational exposure to viny l chloride.