An
estrogen dependency has been suggested for the growth of
fibroadenomas: however, thus far, none of the
steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. In this study, the expression of
estrogen receptor (ER)-alpha and -beta was investigated by immunohistochemistry in 33
fibroadenomas and in 30 benign, three borderline and seven malignant
phyllodes tumors, all with spindle cell growth and in one distant
metastasis. In addition, the presence of ER-beta
mRNA and its variants was evaluated by RT-PCR in microdissected stroma. The possible correlation between
hormone receptor expression and differentiation processes of stromal cells was investigated by smooth muscle actin and
calponin immunostaining. ER-beta was the only
hormone receptor expressed by stroma of
fibroadenomas and
phyllodes tumors, both at
protein and
mRNA level. The highest percentage of ER-beta was observed in
fibroadenomas with cellular stroma and in
phyllodes tumors. In both lesions, ER-beta-positive stromal cells showed expression of smooth muscle actin and/or
calponin, as demonstrated by double immunostaining. In addition, the mean age at diagnosis was significantly lower in patients with ER-beta-positive vs ER-beta-negative
fibroadenomas. In contrast, in
phyllodes tumors, ER-beta expression was higher in older patients. In conclusion, (i) only ER-beta is detected in the stroma of
fibroadenomas and
phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER-beta in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying
fibroadenomas with highly ER-beta-positive stroma cells, may further indicate a
hormone-receptor mechanism involved in regulating the growth of
fibroadenomas. Conversely, the older age of patients with ER-beta-rich
phyllodes tumors suggests that mechanisms, probably independent from
estrogen stimulation, act on the growth of these
tumors.