Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Cancer Sci. 2010 Oct;101(10):2286-92. doi: 10.1111/j.1349-7006.2010.01673.x. Epub 2010 Aug 2.
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 estrogen-producing/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 17β-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.
众所周知，雌激素在乳腺癌细胞增殖中发挥着重要作用。良性乳腺疾病（BBD）包含广泛的疾病谱，其中一些被认为是随后发生乳腺癌的重要危险因素。然而，雌激素在 BBD 中的意义在很大程度上仍不清楚。因此，在本研究中，我们检查了 BBD 中的雌激素组织浓度和产生/代谢雌激素的酶的免疫定位，并将这些发现与正常乳腺和导管原位癌（DCIS）进行了比较。BBD（n=9）中的雌二醇组织浓度显著升高（3.4 倍），高于正常乳腺（n=9），几乎与 DCIS（n=9）相同（0.7 倍）。BBD（n=82）中雌激素硫酸转移酶的免疫反应性明显低于正常乳腺（n=28），但与 DCIS（n=28）无显著差异。芳香酶和类固醇硫酸酯酶的免疫反应性在 BBD 中趋于高于正常乳腺（P=0.07），在绝经后组织中，17β-羟甾类脱氢酶 1 免疫反应性在 BBD 中明显高于正常乳腺。雌激素和孕激素受体的免疫反应性在 BBD 中也明显高于正常乳腺。这些结果表明，BBD 中的雌二醇组织浓度增加到类似于 DCIS 的水平，这主要归因于雌激素硫酸转移酶表达的丧失。由于产生/代谢雌激素的酶的异常表达，BBD 中局部雌二醇浓度的增加可能在雌激素介导的生长的积累和/或随后乳腺癌的发展中发挥重要作用。
