Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses' Health Study.
Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses' Health Study.
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DOI：
10.1038/modpathol.2009.158
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发表时间：
2010-02
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影响因子：
--
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中科院分区：
文献类型：
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雌激素受体-α（ER-α）及其相关基因的表达已成为浸润性乳腺癌分子分类的主要决定因素之一。然而，第二种雌激素受体，雌激素受体β（ER-β）的表达模式，以前没有在一个大的人群为基础的研究中进行评估。因此，我们检测了大量乳腺癌女性患者的ER-β表达，以评估其与浸润性乳腺癌分子分类的关系。我们用3,093例乳腺癌的石蜡块构建了组织微阵列，这些乳腺癌发生在参加护士健康研究的女性中。组织芯片切片进行ER-α、孕酮受体（PR）、人表皮生长因子受体2（HER 2）、细胞角蛋白5/6和表皮生长因子受体（EGFR）的免疫染色。癌症分为管腔A型（ER-α+和/或PR+和HER 2 −）;管腔B型（ER-α+和/或PR+和HER 2+）; HER 2型（ER-α−和PR−和HER 2+）;基底样型（ER-α−、PR−、HER 2 −和EGFR或细胞角蛋白5/6+）。组织微阵列切片也用ER-β的单克隆抗体（ER-β1，克隆PPG 5/1/0，Serotec）免疫染色。分析ER-β表达与浸润性乳腺癌分子分型的关系。总体而言，68%的浸润性乳腺癌为ER-β阳性。ER-β的表达与ER-α（p<0.0001）和PR（p<0.0001）的表达显著相关，与HER 2（p=0.004）、CK 5/6（p=0.02）和EGFR（p=0.006）的表达呈负相关。在具有完整免疫表型数据的2，170例浸润性癌症中，73%为管腔A型，5%为管腔B型，6%为HER 2型，11%为基底细胞样。ER-β表达与分子类型显著相关（p<0.0001），并且在管腔A型（72%的病例）和B型（68%的病例）中比在HER 2或基底样型中更常见。然而，尽管它们被定义为缺乏ER-α表达，但55%的HER 2型和60%的基底细胞样癌显示ER-β表达。ER-β在ER-α表达缺失的浸润性乳腺癌发生发展中的作用值得进一步研究。
The expression of estrogen receptor-alpha (ER-α) and related genes has emerged as one of the major determinants of molecular classification of invasive breast cancers. However, patterns of expression of a second estrogen receptor, estrogen receptor-beta (ER-β), have not been previously evaluated in a large population-based study. Therefore, we examined ER-β expression in a large population of women with breast cancer to assess its relationship to molecular categories of invasive breast cancer. We constructed tissue microarrays from paraffin blocks of 3,093 breast cancers that developed in women enrolled in the Nurses' Health Study. Tissue microarray sections were immunostained for ER-α, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 and epidermal growth factor receptor (EGFR). Cancers were categorized as luminal A (ER-α+ and/or PR+ and HER2−); luminal B (ER-α+ and/or PR+ and HER2+); HER2 (ER-α− and PR− and HER2+); and basal-like (ER-α−, PR−, HER2− and EGFR or cytokeratin 5/6+). Tissue microarray sections were also immunostained with a monoclonal antibody to ER-β (ER-β1, clone PPG5/1/0, Serotec). The relationship between expression of ER-β to molecular class of invasive breast cancer was analyzed. Overall, 68% of the invasive breast carcinomas were ER-β positive. Expression of ER-β was significantly associated with expression of ER-α (p<0.0001) and PR (p<0.0001), and was inversely related to expression of HER2 (p=0.004), CK5/6 (p=0.02) and EGFR (p=0.006). Among 2,170 invasive cancers with complete immunophenotypic data, 73% were luminal A, 5% luminal B, 6 % HER2 and 11% basal-like. ER-β expression was significantly related to molecular category (p<0.0001) and was more common in luminal A (72% of cases) and B (68% of cases) than in HER2 or basal-like types. However, despite their being defined by the absence of ER-α expression, 55% of HER2-type and 60% of basal-like cancers showed expression of ER-β. The role of ER-β in the development and progression of invasive breast cancers defined by lack of expression of ER-α merits further investigation.
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DOI：
10.1073/pnas.96.16.9212
发表时间：
1999-08-03
影响因子：
11.1
作者：
Perou, CM;Jeffrey, SS;Botstein, D
通讯作者：
Botstein, D
影响因子：
11.5
作者：
Shaaban, Abeer M.;Green, Andrew R.;Speirs, Valerie
通讯作者：
Speirs, Valerie
影响因子：
11.5
作者：
Gruvberger-Saal, Sofia K.;Bendahl, Paer-Ola;Fernoe, Marten
通讯作者：
Fernoe, Marten
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Chang, Edmund C.;Frasor, Jonna;Katzenellenbogen, Benita S.
通讯作者：
Katzenellenbogen, Benita S.