VARIATION OF BCL-2 EXPRESSION IN BREAST DUCTS AND LOBULES IN RELATIONTO PLASMA PROGESTERONE LEVELS - OVEREXPRESSION AND ABSENCE OF VARIATION IN FIBROADENOMAS

Some women with benign breast disease eventually develop breast cancer , The mammary gland undergoes tissue remodelling according to hormonal influences, involving a balance between quiescence, proliferation, an d mechanisms of cell death. Proliferation and/or apoptotic events coul d therefore be investigated to help understand the mechanisms of benig n lesion formation and identify mastopathies with a poor prognosis, bc l-2 expression was analysed by immunohistochemistry in 75 benign masto pathies, Protein levels were quantitated with an image analyser in var ious epithelial structures on frozen sections, including adenoses, fib roadenomas, ductal epithelial hyperplasias, cysts, and apparently norm al surrounding lobules and ducts, bcl-2 levels were equivalent in appa rently normal lobules and ducts, as web as In cysts and ductal hyperpl asias. bcl-2 staining was significantly higher in fibroadenomas, known to be of lobular origin [mean=10.1, quantitative immunochemistry scor e (QIC) arbitrary units (AU), n=19], than in normal lobules (mean=5.1 AU, n=43, P=7 x 10(-5)), bcl-2 levels in normal lobules and ducts vari ed according to the menstrual cycle, being higher during the follicula r than the luteal phase (P=1.8 x 10(-2) and P=1.7 x 10(-2), respective ly), This was further supported by a statistical link (P=5 x 10(-3)) b etween high levels of circulating progesterone and weak bcl-2 staining in lobules and dusts, This progesterone-dependent variation was absen t in fibroadenomas. No statistical correlation was found between bcl-2 expression acid circulating levels of oestradiol, and follicle-stimul ating or luteotrophic hormones, Although these are only preliminary re sults, they suggest an influence of progesterone on bcl-2 expression w hich might be lost in fibroadenomas. A hypothesis is proposed concerni ng the potential involvement of altered regulation of the apoptotic pr ocess in the formation of such benign lesions, (C) 1997 John Wiley & S ons, Ltd.