Immunolocalization of estrogen‐producing and metabolizing enzymes in benign breast disease: Comparison with normal breast and breast carcinoma

Abstract

It is well known that estrogens play important roles in the cell proliferation of breast carcinoma. Benign breast disease (BBD) contains a wide spectrum of diseases, and some are considered an important risk factor for subsequent breast carcinoma development. However, the significance of estrogens in BBD has remained largely unknown. Therefore, in this study, we examined tissue concentrations of estrogens and immunolocalization of estrogenproducing ⁄ metabolizing enzymes in BBD, and compared these findings with those in the normal breast and ductal carcinoma in situ (DCIS). Tissue concentration of estradiol in BBD (n = 9) was significantly (3.4-fold) higher than normal breast (n = 9) and nearly the same (0.7-fold) as in DCIS (n = 9). Immunoreactivity of estrogen sulfotransferase in BBD was significantly lower (n = 82) than normal breast (n = 28) but was not significantly different from DCIS (n = 28). Aromatase and steroid sulfatase immunoreactivities tended to be higher (P = 0.07) in BBD than in normal breast, and 17b-hydroxysteroid dehydrogenase type 1 immunoreactivity was significantly higher in BBD than normal breast in the postmenopausal tissues. Immunoreactivity of estrogen and progesterone receptors was also significantly higher in BBD than normal breast. These results suggest that tissue concentration of estradiol is increased in BBD at a level similar to DCIS, which is considered mainly due to loss of estrogen sulfotransferase expression. Increased local estradiol concentration in BBD due to aberrant expression of estrogen-producing ⁄ metabolizing enzymes may play important roles in the accumulation of estradiol-mediated growth and ⁄ or subsequent development of breast carcinoma. (Cancer Sci 2010; 101: 2286-2292 B enign breast disease (BBD) is the most common disorder of the breast in women, and encompasses a wide variety of histological entities.(1,2) Some BBD are considered an important risk factor for subsequent development of breast carcinoma in the same patients. Among the histological subtypes of BBD, atypical ductal hyperplasia (ADH) has the highest (approximately 4-fold) risk of developing breast carcinoma, but patients with common proliferating BBD, such as fibroadenoma (FA), papilloma, sclerosing adenosis (SA), or usual ductal hyperplasia (UDH), are also known to be at increased (approximately 2-fold) risk of malignancy, although controversies have existed. (2)(3)(4) Human breast tissue is a well-known estrogen target tissue. Biologically active estrogen, estradiol, contributes immensely to the growth of breast carcinoma, and endocrine therapy has been used in patients with breast carcinoma to inhibit intratumoral estrogen actions. Benign breast disease frequently expressed estrogen receptor (ER), (5)(6)(7)(8)(9)(10) and women who had used postmenopausal hormonal supplementation were reported to be associated with an increased risk of BBD. (11,12) Treatment with an anti-estrogen tamoxifen significantly reduced the volume and cell proliferation activity of FA (13,14) and The National Surgical Ad...

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