Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers

Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3439-42. doi: 10.1073/pnas.89.8.3439.


Overexpression of the p53 protein, resulting from gene mutations that increase protein stability, has been detected in greater than 25% of primary human breast cancers. In addition, approximately 10% of breast cancer patients have circulating antibodies to the p53 protein. In this study, the anti-p53 humoral response is correlated with the presence and type of mutant p53 protein expressed in the tumor. In a series of 60 breast cancer patients, 0 of 30 tumors with normal, low-level p53 expression induced anti-p53 antibodies, whereas 7 (23%) of 30 tumors with p53 overexpression elicited a specific anti-p53 antibody response. These 7 patients had anti-p53 antibodies that recognized wild-type p53 and a variety of mutant p53 proteins. A comparison of p53 mutations revealed that antibody-negative tumors had mutations exclusively in exons 7 and 8, whereas antibody-positive tumors had mutations primarily in exons 5 and 6. Moreover, all antibody-eliciting tumors contained complexes between p53 and a 70-kDa heat shock protein, whereas none of the antibody-negative tumors contained this complex. This study implicates a 70-kDa heat shock protein in the antigenic presentation of p53.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cell Line
  • Codon
  • Epitopes / analysis
  • Female
  • Genes, p53*
  • Heat-Shock Proteins / immunology*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Immunoblotting
  • Methionine / metabolism
  • Mutation*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Tumor Suppressor Protein p53 / immunology*
  • Tumor Suppressor Protein p53 / metabolism


  • Antibodies, Monoclonal
  • Codon
  • Epitopes
  • Heat-Shock Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Methionine