Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas

Int J Cancer. 1998 Apr 17;79(2):103-10. doi: 10.1002/(sici)1097-0215(19980417)79:2<103::aid-ijc1>;2-x.


Expression of the death-related proteins (DRPs) Bcl-2, Bax, Bcl-x and Bak that regulate cell survival and death was examined using immuno-histochemical methods in a group of 142 T1 (<2 cm) ductal breast carcinomas. Immunostaining results were correlated with loss of apoptosis and clinicopathological parameters such as histological grade (HG) and lymph node involvement. Expression of anti-apoptotic proteins Bcl-2 and Bcl-x was found in 57.0% and 62.75% of tumors, respectively. Bcl-2 expression, but not Bcl-x expression, was related to loss of apoptosis. Expression of the apoptotic proteins Bax and Bak was present in 58% of Bcl-2-negative tumors and associated significantly with an increase in apoptosis. Expression of these DRPs was associated significantly with the HG of the tumors: Bcl-2 and Bak expression was predominant in HG I/II tumors, whereas expression of Bcl-xL and Bax was commonly observed in HG III tumors, as occurs for p53 over-expression. Our results suggest that the loss or gain of apoptosis is regulated tightly in T1 breast carcinomas through the expression of different effectors along with tumor cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology*
  • Cell Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Membrane Proteins / analysis
  • Membrane Proteins / biosynthesis
  • Neoplasm Staging
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein


  • BAK1 protein, human
  • BAX protein, human
  • BCL2L1 protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein