Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer
Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer
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DOI：
10.1073/pnas.1323719111
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发表时间：
2014-02-04
影响因子：
11.1
通讯作者：
Gustafsson, Jan-Ake
中科院分区：
文献类型：
--
作者：
Huang, Bo;Omoto, Yoko;Gustafsson, Jan-Ake
雌激素受体(ER)a在乳腺癌治疗中的作用是明确的，但ERβ1和ERβ2在乳腺中的作用尚不清楚。我们检测了来自两个档案的手术切除的乳腺样本中所有三种受体的表达：(I)来自日本一项研究的187例浸润性导管乳腺癌；(Ii)来自帝国理工学院的20例小叶癌和24例导管癌。样本包括正常区域、增生区、原位癌和浸润性癌。在正常区域，ERα在不超过10%的上皮细胞中表达，而大约80%的上皮细胞表达ERβ。我们发现，导管癌是一种高度增殖、ERα阳性、ERβ阴性的疾病，而小叶癌同时表达ERα和ERβ，但Ki67阳性细胞很少。ERβ2在32%的导管癌中表达，其中83%在绝经后导管癌中表达。在所有ERβ2阳性的癌症中，导管间腔充满致密的胶原，细胞核表达缺氧诱导因子1α。ERβ2的表达不仅限于恶性细胞，而且在间质细胞、免疫细胞和内皮细胞中都很强。在大多数高级别浸润性导管癌中，ERa和ERβ均不表达，而在高级别小叶癌中ERβ缺失，Era和Ki67大量表达。这些数据显示了小叶性和导管性乳腺癌之间ER表达的明显差异，并表明(I)他莫昔芬在晚期可能比早期小叶癌更有效，(Ii)ERβ激动剂在防止原位导管癌变得侵袭性方面具有潜在作用。
The role of estrogen receptor (ER) a as a target in treatment of breast cancer is clear, but those of ER beta 1 and ER beta 2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ER alpha was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ER beta. We found that whereas ductal cancer is a highly proliferative, ER alpha-positive, ER beta-negative disease, lobular cancer expresses both ER alpha and ER beta but with very few Ki67-positive cells. ER beta 2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ER beta 2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1 alpha. ER beta 2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ERa nor ER beta was expressed, but in the high-grade lobular cancer ER beta was lost and ERa and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ER beta agonists in preventing in situ ductal cancers from becoming invasive.