Prognostic significance of TP53 alterations in breast carcinoma

Br J Cancer. 1993 Sep;68(3):540-8. doi: 10.1038/bjc.1993.383.


Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Female
  • Genes, p53*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Oncogene Proteins, Viral / genetics
  • Prognosis
  • Receptor, ErbB-2
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism


  • Oncogene Proteins, Viral
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2