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Development of Antibodies against p53 in Lung Cancer Patients Appears to Be Dependent on the Type of p53 Mutation

Stefan F. Winter, John D. Minna, Bruce E. Johnson, Takashi Takahashi, Adi F. Gazdar and David P. Carbone
Stefan F. Winter
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John D. Minna
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Bruce E. Johnson
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Takashi Takahashi
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Adi F. Gazdar
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David P. Carbone
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DOI:  Published August 1992
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Abstract

Using immunoblotting techniques we studied the sera from small cell lung cancer and non-small cell lung cancer patients for antibodies directed against p53. We have also characterized the majority of these patients' tumors for p53 mutations. In the sera of 13% of the patients (4 of 40 small cell lung cancer and 2 of 6 non-small cell lung cancer) we found antibodies specific for the p53 tumor suppressor gene product. All of the antibody-positive patients tested had p53 missense mutations and expressed detectable p53 antigen in their tumor cell lines. No anti-p53 antibodies were detected in sera from patients whose tumor had p53 stop, splice/stop, splice, or frameshift mutations (n = 10). Thus, while we find that the ability of lung cancer patients to develop anti-p53 antibodies is correlated with the type of p53 mutation, many patients have tumors with missense p53 mutations and did not develop anti-p53 antibodies. The presence of p53 antibodies was not correlated to stage, prior treatment, sex, or survival. None of these lung cancer patient sera had measurable amounts of p53 antigen. By immunoblotting all six anti-p53 antisera we were able to detect a variety of mutant p53 proteins (including those from antibody-negative patients) and detected wild-type p53 protein. The development of anti-p53 antibodies represents an interesting model system for studying immune responses in cancer patients against mutant oncogene products.

Footnotes

  • ↵1 S. F. W. is supported by the Deutsche Forschungsgemeinschaft.

  • ↵2 Present address: Aichi Cancer Center, Research Institute, Laboratory of Chemotherapy, Kanokoden, Chikusa-ku, Nagoya 464, Japan.

  • ↵3 Present address: Abteilung fuer Haematologie und Onkologie, Universita-etsklinikum Marburg, Baldingerstrasse, 3550 Marburg/L., Germany. To whom requests for reprints should be addressed, at Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8593.

  • Received October 31, 1991.
  • Accepted May 15, 1992.
  • ©1992 American Association for Cancer Research.
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August 1992
Volume 52, Issue 15
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Development of Antibodies against p53 in Lung Cancer Patients Appears to Be Dependent on the Type of p53 Mutation
Stefan F. Winter, John D. Minna, Bruce E. Johnson, Takashi Takahashi, Adi F. Gazdar and David P. Carbone
Cancer Res August 1 1992 (52) (15) 4168-4174;

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Development of Antibodies against p53 in Lung Cancer Patients Appears to Be Dependent on the Type of p53 Mutation
Stefan F. Winter, John D. Minna, Bruce E. Johnson, Takashi Takahashi, Adi F. Gazdar and David P. Carbone
Cancer Res August 1 1992 (52) (15) 4168-4174;
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