Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast

Abstract

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)-a and -b 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-b 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-b was the only hormone receptor expressed by stroma of fibroadenomas and phyllodes tumors, both at protein and mRNA level. The highest percentage of ER-b was observed in fibroadenomas with cellular stroma and in phyllodes tumors. In both lesions, ER-b-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-b-positive vs ER-b-negative fibroadenomas. In contrast, in phyllodes tumors, ER-b expression was higher in older patients. In conclusion, (i) only ER-b 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-b in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER-b-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-b-rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.

486 From the 1 Department of Pathology, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, 2 Department of Surgery, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, 3 Department of Anatomy, Faculty of Medicine, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia Received: Jan. 18, 2011; Accept: Mar. 8, 2012 Correspondence to: Dr. Siti Aishah Md Ali, Department of Pathology, Faculty of Medicine, University

“…A study reported that ERα was mainly expressed by epithelia cells while no expression in the stromal cells [15] compared to the present study, only 7.1% ERα expression in malignant PT and absent in borderline and benign PT. Previous studies demonstrated that ERb was found in stromal cells in the FA and PT.…”

“…Previous studies demonstrated that ERb was found in stromal cells in the FA and PT. [13,15] We opine that ERb showed better expression than ERα which was highly detectable in the stromal component. The greater expression of ERb suggests that it may be the main ER in the breast.…”

“…[10] Proliferation of fibroepithelial tumor is mainly in the stromal component, followed by proliferation of epithelia cells. [15] The stromal elements were considered as the neoplastic component and therefore believed as the determinant of biological activity. [27] The known Bcl2 protein is usually expressed in normal tissue and benign proliferative lesions, as they discourage the promotion of cell proliferation by inhibit apoptosis.…”

“…[13] ERα was reported to express mainly by epithelial cells in fibroepithelial tumors, while was commonly difficult to define the presence of ERα in the stroma component. [15] Ki-67 antigen is a cell proliferation-related protein that can be detected with monoclonal antibody MIB-1 and to evaluate proliferative activity in different types of tumor. [16,17] Ki-67 is linked to cell cycle specially expresses during late G1, S, M and G2 phase of the cell cycle, is undetected in cells of the G0 phase.…”

Simultaneous automatic scoring and co‐registration of hormone receptors in tumor areas in whole slide images of breast cancer tissue slides

“…In addition, for ER/PR scoring, we are only interested in the staining that occurs to tumour nuclei. On occasion the IHC stain binds to non-tumour nuclei, [13][14][15] but this has no relevance to the score and should be ignored. Therefore, to ensure that only the correct parts of the tissue are being scored, the tumour nuclei must be isolated from the remaining tissue.…”