Shaaban Abeer M, Green Andrew R, Karthik Suchita, Alizadeh Yalda, Hughes Thomas A, Harkins Lynn, Ellis Ian O, Robertson John F, Paish Emma C, Saunders Philippa T K, Groome Nigel P, Speirs Valerie
YCR and Liz Dawn Pathology and Translational Sciences Centre, Leeds Teaching Hospitals and Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.
Clin Cancer Res. 2008 Aug 15;14(16):5228-35. doi: 10.1158/1078-0432.CCR-07-4528.
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 ERbeta1, ERbeta2, and ERbeta5 by immunohistochemistry in a large cohort of breast carcinomas with long-term follow-up.
Tissue microarrays were stained with ERbeta1, ERbeta2, and ERbeta5 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).
Nuclear ERbeta2 and ERbeta5, but not ERbeta1, significantly correlated with OS (P = 0.006, P = 0.039, and P = 0.099, respectively), and ERbeta2 additionally with DFS (P = 0.013). ERbeta2 also predicted response to endocrine therapy (P = 0.036); correlated positively with ERalpha, progesterone receptor, androgen receptor, and BRCA1; and correlated inversely with metastasis and vascular invasion. Tumors coexpressing ERbeta2 and ERalpha had better OS and DFS. Cytoplasmic ERbeta2 expression, alone or combined with nuclear staining, predicted significantly worse OS. Notably, patients with only cytoplasmic ERbeta2 expression had significantly worse outcome (P = 0.0014).
This is the first study elucidating the prognostic role of ERbeta1, ERbeta2, and ERbeta5 in a large breast cancer series. ERbeta2 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 ERalpha.
先前关于雌激素受体（ER）-β在乳腺癌中预后意义的研究结果相互矛盾，这可能是由其存在的五种亚型所致。我们的目的是通过免疫组织化学方法，在一大组接受长期随访的乳腺癌患者中，阐明ERβ1、ERβ2和ERβ5的预后意义。
组织微阵列用ERβ1、ERβ2和ERβ5抗体进行染色，并根据阳性肿瘤细胞的百分比和使用Allred系统进行评分。对细胞核和细胞质染色进行评估，并与组织病理学特征、总生存期（OS）和无病生存期（DFS）进行关联分析。
细胞核ERβ2和ERβ5，而非ERβ1，与OS显著相关（P分别为0.006、0.039和0.099），ERβ2还与DFS相关（P = 0.013）。ERβ2还可预测内分泌治疗反应（P = 0.036）；与ERα、孕激素受体、雄激素受体和BRCA1呈正相关；与转移和血管侵犯呈负相关。同时表达ERβ2和ERα的肿瘤具有更好的OS和DFS。细胞质ERβ2表达，单独或与细胞核染色结合，预测OS显著更差。值得注意的是，仅细胞质表达ERβ2的患者预后显著更差（P = 0.0014）。
这是第一项在大型乳腺癌系列研究中阐明ERβ1、ERβ2和ERβ5预后作用的研究。ERβ2是乳腺癌中一个强有力的预后指标，但细胞核和细胞质表达对预后的影响不同。在临床乳腺癌中检测这些指标可以更全面地了解患者的预后情况，补充ERα的评估。
