P. Roger et al., Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors, CANCER RES, 61(6), 2001, pp. 2537-2541
To understand the significance of estrogen receptor beta (ER beta) in mamma
ry carcinogenesis, we evaluated the expression of ER beta in preinvasive ma
mmary tumors. The percentage of ER beta -positive epithelial. or tumoral ce
lls mas assayed by quantitative immunohistochemistry using an image analyze
r in 130 lesions of varying histological risk from 118 patients [71 with be
nign breast disease (BBD) and 59 with carcinoma in situ (CIS)] and compared
with 118 adjacent histologically normal glands. Five groups of lesions wit
h an increasing risk of invasive cancer, from BED without hyperplasia to hi
gh-grade CIS, were studied, Results were compared with ER alpha and Ki67 im
munostaining, The percentage of ER beta -positive cells was high (median, 8
5%) in "normal" mammary glands and in nonproliferative BED and decreased si
gnificantly (P < 0.0001) in proliferative BED without atypia and in CIS, co
ntrasting,vith an inverse progression for the ER<alpha> level. In normal ma
mmary glands, the ER beta level did not vary according to the nature of the
lesion at the periphery and was significantly higher (P < 0.007) than in a
djacent preinvasive lesions, except in nonproliferative BED. The ER<beta> l
evel decreased in proliferative BED, anticipating the ER alpha increase, wh
ich was significant in BED with atypia, In high-grade ductal carcinoma irt
situ, both ER levels were low, The ratio between ER beta and ER alpha was h
igh in normal glands, and decreased significantly in proliferative lesions.
ER beta staining was inversely correlated with Ki67 (r = -0.333; P < 0.001
), more particularly in high-grade ductal carcinoma in situ (r = -0.57; P <
0.02), The marked and early decreased level of ER beta protein associated
with other criteria of cell proliferation suggests a protective effect of E
R beta against the mitogenic activity of estrogens in mammary premalignant
lesions. Knowledge of the ER beta and ER alpha content in each preinvasive
lesion should help to rationalize antiestrogen preventive therapy adapted t
o each individual patient.