Immunocytochemical Localization of BCL-2 Protein in Human Breast Cancers and Its Relationship to a Series of Prognostic Markers and Response to Endocrine Therapy

Int J Cancer. 1994 Dec 1;59(5):619-28. doi: 10.1002/ijc.2910590508.

Abstract

The protein product of the bcl-2 gene is though to be involved in inhibition of apoptosis; it may therefore be important in the modulation of hormonal/anti-hormonal responsiveness exhibited by tumours. This study immunocytochemically investigates (i) relationships between bcl-2 protein expression in primary breast cancers and other markers of prognostic and therapeutic value and (ii) associations of the bcl-2 protein with breast cancer responsiveness to endocrine therapy. The bcl-2 protein was found within the tumour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter-patient staining was heterogeneous. Immunostaining for steroid hormone receptors was strongly associated with that for the bcl-2 protein, and it is thus possible that this protein, like progesterone receptor, is under oestrogen regulation via oestrogen receptor. The protein was inversely related to 2 markers of endocrine insensitivity, epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein, while no associations were observed with either transforming growth factor (TGF)-alpha or Ki-67 proliferative status. A highly significant relationship was observed between response to endocrine therapy and the presence of bcl-2 protein. Indeed, bcl-2 immunostaining proved to be a more accurate predictor of response than oestrogen receptor status. Patients with elevated bcl-2 immunostaining (particularly those who coexpressed high oestrogen receptor levels) appeared to derive the greatest benefit from endocrine therapy. Our results are paradoxical since it was expected that the bcl-2 protein would counteract the tumour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy
  • Cell Nucleus / chemistry
  • Cytoplasm / chemistry
  • Epithelium / chemistry
  • ErbB Receptors / analysis
  • Female
  • Goserelin / therapeutic use*
  • Humans
  • Immunoenzyme Techniques
  • Prognosis
  • Proto-Oncogene Proteins / analysis*
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Tamoxifen / therapeutic use*
  • Transforming Growth Factor alpha / analysis

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Transforming Growth Factor alpha
  • Tamoxifen
  • Goserelin
  • ErbB Receptors