Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy.
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.
Breast Cancer Unit, University of Wales College of Medicine, Cardiff, UK.
J M
JM
Gee
J F
JF
Robertson
I O
IO
Ellis
P
P
Willsher
R A
RA
McClelland
H B
HB
Hoyle
S R
SR
Kyme
P
P
Finlay
R W
RW
Blamey
R I
RI
Nicholson
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004848:Epithelium / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D007124:Immunoenzyme Techniques; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016211:Transforming Growth Factor alpha / Q000032:analysis
D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016211:Transforming Growth Factor alpha; D013629:Tamoxifen; D017273:Goserelin; D066246:ErbB Receptors