Immune response against thep53 tumor suppressor gene product: Clinical studies and molecular mechanisms

In this study the immune response against the p53 tumor suppressor protein was investigated. The development of quantitative immunoassays for measuring p53 antibody titers in serum allowed the performance of an extensive study for p53 autoantibody generation in 1392 patients with 13 different malignancies. Patients with colon and ovarian cancer develop antibodies against p53 with higher frequencies than patients with other types of tumors. Analysis of serum samples from blood donors and healthy volunteers demonstrated the high specificity of this test ({dollar}>{dollar}98%).; Serum p53 autoantibodies are indicators of unfavorable outcome in ovarian and breast cancers, but have no prognostic value in colon cancer. p53 antibody titers fluctuated with time in parallel with other conventional tumor markers, reflecting changes in disease status. Based on this observation I suggest that monitoring cancer patients with serum p53 may have clinical utility, especially in those whose tumors do not produce conventional tumor markers, like CEA or CA-125. Further, p53 autoantibodies were present in the ascites fluid of 20% of ovarian cancer patients. p53 protein was detected in the ascites fluid of 7% of these patients. This is the first identification of p53 protein in a biological fluid.; p53 antibodies were found more frequently in sera of patients with tumors expressing high levels of p53 protein (p = 0.05). However, not all patients with tumors overexpressing p53 developed p53 antibodies, and not all p53 antibody-positive patients had p53 overexpression in their tumors. p53 antibody-positive patients did not have higher frequency of p53 gene mutations than p53 antibody-negative patients. The former were associated with a Tyr substitution in the protein product.; These studies on the immunological and molecular aspects of p53 autoantibody generation in cancer contribute to the better understanding of this immune reaction of the host against cancer, and offer possibilities for cancer monitoring and possibly diagnosis.