Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications

J Pathol. 1999 Jan;187(2):207-16. doi: 10.1002/(SICI)1096-9896(199901)187:2<207::AID-PATH223>3.0.CO;2-U.


Various new prognostic indicators have been identified for mammary carcinomas, but the issue of their significance remains unsettled. The prognostic impact of p53, c-erbB-2, and topoisomerase II alpha expression was investigated in relation to standard prognostic factors for carcinomas of the breast and to the tumour cell growth fraction. Paraffin-embedded specimens of 356 node-negative infiltrating ductal carcinomas were stained immunohistochemically using a polyclonal antiserum to c-erbB-2, and the monoclonal antibodies DO-1 (p53), Ki-S4 (topoisomerase II alpha), and Ki-S5 (Ki-67). The patients were followed for a median duration of 99 months. Both p53 and c-erbB-2 were significantly associated with high tumour grade, large tumour size, DNA aneuploidy, lack of steroid hormone receptors, young age, and increased topoisomerase II alpha and Ki-67 expression levels. The correlation of p53 and c-erbB-2 was not significant. Topoisomerase II alpha and Ki-67 scores closely paralleled each other, indicating that both reflect the proliferative activity of tumour cells. A univariate analysis of overall (OS), specific (SS), and disease-free survival (DFS) revealed all the above-mentioned parameters to be statistically significant except patient age, which was relevant only to overall survival. Multivariate analysis with inclusion of all covariates selected tumour size and proliferation (topoisomerase II alpha and Ki-67) indices as independent predictors of survival in all three models. No additional information was gained by p53 or c-erbB-2. It is concluded that the proliferative activity, as assessed by topoisomerase II alpha or Ki-67 immunostaining, is the most useful indicator of breast cancer prognosis, except for tumour size.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Division
  • DNA Topoisomerases, Type II* / metabolism
  • DNA-Binding Proteins
  • Female
  • Follow-Up Studies
  • Humans
  • Isoenzymes / metabolism
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Ploidies*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate
  • Tumor Suppressor Protein p53 / metabolism


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Isoenzymes
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II