Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade

J Pathol. 2003 Dec;201(4):573-80. doi: 10.1002/path.1486.


Ductal carcinoma in situ (DCIS) of the breast is an early, non-invasive lesion and the prognosis is associated with the extent of necrosis and cell death within the tumour. Two cell death genes, BNip3 and NIX, are up-regulated in response to hypoxia in breast carcinoma cells, although any involvement of either gene in disease progression is currently unknown. This study has analysed the expression of BNip3 and NIX in 56 samples of breast DCIS, as well as in adjacent benign and invasive breast tissue. Both genes are strongly expressed in the epithelial component of a subset of DCIS and invasive disease. The data show a correlation between high expression of BNip3 in the DCIS cells and a high-grade, necrotic lesion that is likely to be associated with invasive tumour. BNip3 was present in tumour-associated macrophages and in apocrine metaplastic lesions. Expression of NIX did not correlate with any of the parameters investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma in Situ / genetics*
  • Carcinoma in Situ / pathology
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology
  • Cell Death / genetics*
  • Epithelium / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Macrophages / pathology
  • Membrane Proteins / genetics*
  • Necrosis
  • Neoplasm Invasiveness / genetics
  • Oxygen / physiology
  • Proto-Oncogene Proteins*
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Tumor Suppressor Proteins*


  • BNIP3 protein, human
  • BNIP3L protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Tumor Suppressor Proteins
  • Oxygen