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Analysis of p53 Antibodies in Patients with Various Cancers Define B-Cell Epitopes of Human p53: Distribution on Primary Structure and Exposure on Protein Surface¹

Unité 301 INSERM, Institut de Génétique Moléculaire [R. L., B. S., T. S.] and Services de Pneumologie [G. Z., J. T., A. H.] and d'Urologie [F. D., A. L.], and Laboratoire d'Immunologie et d'Histocompatibilité [D. B.], Hôpital St. Louis, 75010 Paris; Unité d'Oncologie, IRSC, 94802 Villejuif [C. C.]; Laboratoire d'Hématologie, CHU, Lille [C. P., P. F.]; Service d'Urologie, Hôpital Morvan, 29200, Brest [G. F., P. M.]; Service des Maladies du Foie et de l'Appareil Digestif, Hôpital de Bicêtre, 94275, Le Kremlin Bicêtre [P. L., G. P.]; Department of Nuclear Medicine, Institut Gustave Roussy, 94805 Villejuif [M. S.]; Centre Oscar Lambret, BP307, 59020 Lille [J. P. P.]; and Unité de Diagnostic Moléculaire, Institut Gustave Roussy, 94805 Villejuif [N. J., B. B.], France

p53 antibodies have been found in sera of patients with breast and lung carcinomas and in children with B-lymphomas. We report here the presence of p53 antibodies in sera of patients with 11 different types of cancer. The frequency of seropositives for p53 varied among the different types of cancer, but a correlation with the frequency of p53 gene alteration was established. Using a powerful peptide enzyme-linked immunosorbent assay, we demonstrated that the immune response of patients with p53 antibodies was restricted to a small subset of peptides localized in the amino and carboxy termini of p53, whatever the type of cancer. Given the similarities of the patterns of immune responses in patients with p53 antibodies and animals hyperimmunized with human p53, we propose that the p53 humoral response is the result of a self-immunization process which is itself the consequence of p53 protein accumulation in tumor cells.

¹ This work was supported by grants from the Association de Recherche sur le Cancer, Ligue Nationale contre le Cancer, and the Fédération Nationale des Groupements des Entreprises Françaises dans la Lutte contre le Cancer.

² Supported by fellowships from the French Ministère de la Recherche et de la Technologie and Société Française du Cancer; present address: University of Gdansk, Department of Biochemistry, Gdansk, Poland.

³ Present address: U248 INSERM, 10 av. de Verdun, 75010 Paris, France.

⁴ Present address: Service d'urologie, CHI Brabois, 54500 Vandoeuvre les Nancy, France.

⁵ To whom requests for reprints should be addressed, at Unité 301 INSERM, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France.

Received 9/20/93. Accepted 11/ 2/93.

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