Nuclear and cytoplasmic expression of ERβ1, ERβ2, and ERβ5 identifies distinct prognostic outcome for breast cancer patients
Nuclear and cytoplasmic expression of ERβ1, ERβ2, and ERβ5 identifies distinct prognostic outcome for breast cancer patients
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DOI：
10.1158/1078-0432.ccr-07-4528
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发表时间：
2008-08-15
影响因子：
11.5
通讯作者：
Speirs, Valerie
中科院分区：
文献类型：
--
作者：
Shaaban, Abeer M.;Green, Andrew R.;Speirs, Valerie
目的：以前关于雌激素受体（ER）-β在乳腺癌中的预后意义的相互矛盾的结果可以通过亚型的贡献来解释，其中存在五种亚型。我们的目的是阐明ER β 1、ER β 2和ER β 5在一个大的乳腺癌队列中的预后意义，并进行长期随访。实验设计：用ER β 1、ER β 2和ER β 5抗体对组织微阵列进行染色，并使用Allred系统对阳性肿瘤细胞的百分比进行评分。评估细胞核和细胞质染色，并将其与组织病理学特征、总生存期（OS）和无病生存期（DFS）相关。结果如下：细胞核ER β 2和ER β 5与OS显著相关（分别为P = 0.006、P = 0.039和P = 0.099），ER β 2与DFS显著相关（P = 0.013），但ER β 1与OS无关。ER β 2还可预测内分泌治疗的疗效（P = 0.036），与ER α、孕激素受体、雄激素受体和BRCA 1呈正相关，与转移和血管浸润呈负相关。共表达ER β 2和ER α的肿瘤具有更好的OS和DFS。细胞质ER β 2表达，单独或与细胞核染色相结合，预测OS显著更差。值得注意的是，仅细胞质ER β 2表达的患者预后显著更差（P = 0.0014）。结论：这是首次阐明ER β 1、ER β 2和ER β 5在大型乳腺癌系列中的预后作用的研究。ER β 2是乳腺癌的一个强有力的预后指标，但细胞核和细胞质表达对结果的影响不同。在临床乳腺癌中测量这些可以提供更全面的患者结果，补充ER α。
Purpose: Previous conflicting results about the prognostic significance of estrogen receptor (ER)-beta in breast cancer may be explained by contribution of isoforms, of which five exist. Our aim was to elucidate the prognostic significance of ER beta 1, ER beta 2, and ER beta 5 by immunohistochernistry in a large cohort of breast carcinomas with long-term follow-up. Experimental Design:Tissue microarrays were stained with ER beta 1, ER beta 2, and ER beta 5 antibodies and scored as percentage of positive tumor cells and using the Allred system. Nuclear and cytoplasmic staining was evaluated and correlated with histopathologic characteristics, overall survival (OS) and disease-free survival (DFS). Results: Nuclear ER beta 2 and ER beta 5, but not ER beta 1, significantly correlated with OS (P = 0.006, P = 0.039, and P = 0.099, respectively), and ER beta 2 additionally with DFS (P = 0.013). ER beta 2 also predicted response to endocrine therapy (P = 0.036); correlated positively with ER alpha, progesterone receptor, androgen receptor, and BRCA1; and correlated inversely with metastasis and vascular invasion. Tumors coexpressing ER beta 2 and ER alpha had better OS and DFS. Cytoplasmic ER beta 2 expression, alone or combined with nuclear staining, predicted significantly worse OS. Notably, patients with only cytoplasmic ER beta 2 expression had significantly worse outcome (P = 0.0014). Conclusions: This is the first study elucidating the prognostic role of ER beta 1, ER beta 2, and ER beta 5 in a large breast cancer series. ER beta 2 is a powerful prognostic indicator in breast cancer, but nuclear and cytoplasmic expression differentially affect outcome. Measuring these in clinical breast cancer could provide a more comprehensive picture of patient outcome, complementing ER alpha.