Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion

Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7262-6. doi: 10.1073/pnas.89.15.7262.


Twenty-seven cases of inflammatory breast cancer were screened for the presence of the p53 protein by immunocytochemical methods using a monoclonal antibody directed against the p53 protein. Three groups were detected: 8 cases (30%) had high levels of p53 in the nucleus of the cancer cells; 9 cases (33%) had a complete lack of detectable staining; 10 cases (37%) showed a pattern of cytoplasmic staining with nuclear sparing. Nucleotide sequence analysis of p53 cDNAs derived from the samples with cytoplasmic staining revealed only wild-type p53 alleles in 6 out of 7 cases. An eighth case was determined to be wild type by a single-strand conformation polymorphism. In contrast, the samples containing nuclear p53 contained a variety of missense mutations and a nonsense mutation. The p53 cDNAs from 3 of the tumors that lacked detectable p53 staining were analyzed, and all 3 had wild-type nucleotide sequences. Interestingly, a case of normal lactating breast tissue also showed intense cytoplasmic staining for p53 with nuclear sparing. These data suggest that some breast cancers that contain the wild-type form of p53 protein may inactivate its tumor-suppressing activity by sequestering this protein in the cytoplasm, away from its site of action in the cell nucleus. The detection of cytoplasmic p53 in normal lactating breast tissue could suggest that this is the mechanism employed in specific physiological situations to permit transient cell proliferation. This observation could explain how some breast cancer tissues inactivate p53 function without mutation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Biomarkers, Tumor / analysis
  • Breast / cytology
  • Breast / physiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Nucleus / physiology*
  • Cell Nucleus / ultrastructure
  • Codon
  • DNA, Neoplasm / genetics
  • Exons
  • Female
  • Gene Expression
  • Genes, p53
  • Humans
  • Immunohistochemistry
  • Lactation
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogenes
  • RNA, Neoplasm / genetics
  • Receptor, ErbB-2
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Reference Values
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics*


  • Biomarkers, Tumor
  • Codon
  • DNA, Neoplasm
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • RNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2