EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival

J Pathol. 2002 Jan;196(1):17-25. doi: 10.1002/path.1003.


One hundred patients with breast carcinoma followed for 7-11 years were included in the present study of EGFR family members, using immunohistochemistry and RT-PCR. By immunohistochemistry, 36%, 27%, 26%, and 82% of the tumours were positive for EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. All the immunoreactive tumours were confirmed positive by RT-PCR. Tumour size, histological grade, lymph node status, S-phase fraction, and stage were confirmed to be significantly associated with both disease-free and cancer-specific survival in the present study. Methods of treatment, histological type, and ploidy had no significant effect on survival. Statistical analysis of EGFR family members in these tumours showed a significant association between c-erbB-2 expression and reduced disease-free and cancer-specific survival. c-erbB-4 expression was associated with a more favourable outcome. Co-expression of c-erbB-2 and EGFR was associated with a worse prognosis. c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. In conclusion, c-erbB-2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. However, c-erbB-4 antagonizes the c-erbB-2 effect on clinical course in breast carcinomas. To achieve best results with immunotherapy against the c-erbB-2 receptor, clarifying the status of c-erbB-4 expression may be of significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • ErbB Receptors / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-3 / metabolism
  • Receptor, ErbB-4
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate


  • Biomarkers, Tumor
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4