Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy

✍ Scribed by Julia M. W. Gee; John F. R. Robertson; Ian O. Ellis; Peter Willsher; Richard A. McClelland; Helen B. Hoyle; Susan R. Kyme; Pauline Finlay; Roger W. Blamey; Robert I. Nicholson

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 824 KB
• Volume: 59
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910590508

✦ Synopsis

The protein product of the bcl-2 gene is thought 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 turnour epithelial cell cytoplasm of 32/46 breast cancer specimens; inter-patient staining was heterogeneous. lmmunostaining 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 imrnunostaining 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 turnour inhibitory effects of endocrine therapies as it is thought to prevent programmed cell death.