Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer

Int J Cancer. 1991 Nov 11;49(5):650-5. doi: 10.1002/ijc.2910490504.


c-erbB-2 protein over-expression was studied immunohistochemically in 319 paraffin-embedded breast carcinomas representing 89% of all breast-cancer cases operated in the Tampere University Hospital between 1977 and 1981. The immunohistochemical evaluation of c-erbB-2 was optimized using protease pre-treatment and verified using antibodies for both the external and the internal domains of the protein. c-erbB-2 over-expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade (p less than 0.0001), DNA aneuploidy (p = 0.003), high tumor S-phase fraction (p less than 0.0001), and lack of estrogen (p less than 0.0001) and progesterone (p = 0.03) receptors. Overall, breast-cancer patients with c-erbB-2 over-expression had about 2.2-fold relative risk (RR) of death (p less than 0.001) as compared with those without over-expression. According to a multivariate analysis, c-erbB-2 over-expression was an independent prognostic factor in the whole material as well as in the node-negative sub-set. In node-negative breast-cancer tumor size, S-phase and c-erbB-2 status defined a large patient group with only 4% 5-year and 15% 10-year mortality rate without adjuvant therapy. In comparison with c-erbB-2-negative tumors, those with over-expression of this gene metastasized 3 times more often (p = 0.0002) to the lungs, liver and brain and 3 times less often to the bone. Our findings suggest that the prognostic value of c-erbB-2 over-expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Division
  • DNA / analysis
  • Female
  • Gene Amplification
  • Gene Expression*
  • Humans
  • Immunoenzyme Techniques
  • Menopause
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Ploidies
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Receptor, ErbB-2
  • Risk Factors
  • Survival Rate


  • Proto-Oncogene Proteins
  • DNA
  • Receptor, ErbB-2