Neu-protein Overexpression in Breast Cancer. Association With Comedo-Type Ductal Carcinoma in Situ and Limited Prognostic Value in Stage II Breast Cancer

N Engl J Med. 1988 Nov 10;319(19):1239-45. doi: 10.1056/NEJM198811103191902.


Amplification of the neu proto-oncogene in breast cancer has been reported to correlate with the presence of lymph-node metastases and with a poor prognosis. We describe a method for the immunohistochemical detection of overexpression of neu protein on formalin-fixed paraffin-embedded tissue, with the use of two different monoclonal antibodies. In a group of tumors with a known neu-gene copy number, intense membrane staining of tumor cells was present in all tumors with neu-gene amplification. Of 189 tumors from patients with Stage II breast cancer, 27 (14 percent) had neu-membrane staining. Neu overexpression was associated with larger tumor size (P = 0.006) but not with lymph-node involvement. Neu-protein expression in lymph-node metastases was the same as its expression in primary tumors. Among the patients with neu overexpression (median follow-up, 37 months), disease-free survival was not significantly shorter; overall survival was reduced significantly in these patients (P = 0.042), but this reduction did not remain significant after adjustment for tumor size. Of 45 ductal carcinomas in situ, 19 (42 percent) had neu-membrane staining. These 19 were all of the large-cell, comedo growth type. None of 16 ductal carcinomas in situ of small-cell, papillary, or cribriform growth type had neu overexpression. We conclude that neu overexpression may be an early step in the development of a distinct histologic type of carcinoma of the breast, but we could find no association of overexpression with lymph-node status or tumor recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Carcinoma in Situ / diagnosis*
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / pathology
  • Carcinoma, Intraductal, Noninfiltrating / diagnosis*
  • Carcinoma, Intraductal, Noninfiltrating / genetics
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Female
  • Gene Amplification
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Precipitin Tests
  • Prognosis
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogenes*
  • Receptor, ErbB-2
  • Transfection


  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Receptor, ErbB-2