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

Using ¡mmunoblottingtechniques we studied the sera from small celllung cancer and non-small cell lung cancer patients for antibodies directed against p53. We have also characterized the majority of thesepatients' 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. Allof the antibody-positive patients tested had p53 missense mutations andexpressed detectable p53 antigen in their tumor cell lines. No anti-p53antibodies were detected in sera from patients whose tumor had p53stop, splice/stop, splice, or frameshift mutations (n = 10). Thus, whilewe find that the ability of lung cancer patients to develop anti-p53antibodies is correlated with the type of p53 mutation, many patientshave tumors with missense p53 mutations and did not develop anti-p53antibodies. The presence of p53 antibodies was not correlated to stage, prior treatment, sex, or survival. None of these lung cancer patient serahad measurable amounts of p53 antigen. By immunoblotting all sixanti-pS3 antisera we were able to detect a variety of mutant p53 proteins(including those from antibody-negative patients) and detected wild-typep53 protein. The development of anti-p53 antibodies represents an interesting model system for studying immune responses in cancer patients against mutant oncogene products.