Expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast

Virchows Arch. 2002 Nov;441(5):449-55. doi: 10.1007/s00428-002-0691-0. Epub 2002 Jul 24.


Molecular evidence has recently suggested a number of different pathways leading to the development of ductal carcinoma of the breast. The links between atypical ductal hyperplasia and low-grade ductal carcinoma in situ and lobular neoplasia and lobular carcinoma are well known pathologically, but high-grade in situ and invasive carcinomas appear to have a different biological oncogenetic pathway. Morphologically there is a similarity between apocrine cells and some cases of high-grade ductal carcinoma. In order to investigate this possibility a number of different biological markers known to occur in high-grade breast carcinomas were assessed in both apocrine metaplasia (APM) and a putative premalignant lesion called apocrine change within sclerosing adenosis (AA). In 64 cases of APM and 18 cases of AA we examined for expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 proteins using immunocytochemistry. c-erbB2 expression was seen in 55.6% of AA cases and in 10.9% of APM cases. p53 expression was detected in 27.8% of AA cases but only 1.6% of APM cases. All cases of AA and APM were negative for the anti-apoptotic protein Bcl-2, but all the APM and 33.3% of AA cases showed cytoplasmic positivity for Bax, a pro-apoptotic protein. All the cases of AA and APM were positive for c-myc oncoprotein, however, the mean percentage of nuclear positivity was 50% in AA and 37% in cases of APM cases. The mean percentage positivity for Ki-67, a proliferation associated antigen, was 3.6% in AA and 1.3% in APM. The results indicate that a subset of breast lesions containing APM epithelium show abnormal oncoprotein and apoptosis-related protein expression and have a higher proliferation rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apocrine Glands / metabolism*
  • Apocrine Glands / pathology
  • Biomarkers* / analysis
  • Female
  • Fibrocystic Breast Disease / metabolism*
  • Fibrocystic Breast Disease / pathology
  • Humans
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Metaplasia / pathology
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / analysis
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / metabolism
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Biomarkers
  • Ki-67 Antigen
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Receptor, ErbB-2