Department of Histopathology, Nottingham City Hospital, School of Molecular Medical Sciences, The University of Nottingham and Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, NG5 1PB, UK.
Breast Cancer Res Treat. 2013 Jul;140(2):307-16. doi: 10.1007/s10549-013-2614-y. Epub 2013 Jul 26.
The coactivator-associated arginine methyltransferase-1 (CARM1) is implicated in regulation of oestrogen receptor (ER) α-mediated gene pathways in response to ER activation. It plays an important role in breast cancer growth by regulating the E2F1 expression suggesting that CARM1 could be a target in the subclassification of oestrogen-dependent breast cancer. This study aims to investigate the clinical and biological importance of CARM1 protein expression in a large (1,130 patients), well-characterised and annotated series of invasive breast cancers using tissue microarrays and immunohistochemistry. In the whole series, increased CARM1 expression is correlated with features associated with aggressive behaviour such as young age, premenopausal status, large tumour size and high tumour grade. There is a positive correlation between CARM1 expression and biomarkers associated with non-luminal phenotype and poor prognosis such as HER2, basal cytokeratins, EGFR, p53 and the proliferation markers Ki67, TK1, CD71 and Cyclin E. Negative associations with the luminal-associated markers including steroid receptors and luminal cytokeratins are found. Similar associations are identified in the ER-positive/luminal subgroup (n = 767). Outcome analyses indicate that CARM1 expression is an independent predictor of shorter breast cancer-specific survival and disease-free interval in the whole series and in the ER-positive subgroup. CARM1 shows an oncogenic effect in breast cancer and its expression is associated with poor prognosis. CARM1 could be a potential marker of luminal class subclassification and for target therapy, particularly in the ER-positive luminal-like subgroup.
辅激活因子相关精氨酸甲基转移酶-1(CARM1)参与调节雌激素受体(ER)α介导的基因通路,以响应 ER 激活。它通过调节 E2F1 的表达在乳腺癌生长中发挥重要作用,提示 CARM1 可能是雌激素依赖性乳腺癌亚分类的靶点。本研究旨在使用组织微阵列和免疫组织化学方法,在一个大型(1130 例)、特征良好且注释的浸润性乳腺癌系列中,研究 CARM1 蛋白表达的临床和生物学重要性。在整个系列中,CARM1 表达增加与侵袭性行为相关的特征相关,例如年轻、绝经前状态、肿瘤较大和高肿瘤分级。CARM1 表达与非腔型表型和不良预后相关的生物标志物呈正相关,如 HER2、基底细胞角蛋白、EGFR、p53 以及增殖标志物 Ki67、TK1、CD71 和细胞周期蛋白 E。与腔型相关标志物包括甾体受体和腔细胞角蛋白呈负相关。在 ER 阳性/腔型亚组(n=767)中也发现了类似的相关性。生存分析表明,CARM1 表达是整个系列和 ER 阳性亚组乳腺癌特异性生存和无病间隔较短的独立预测因子。CARM1 在乳腺癌中具有致癌作用,其表达与预后不良相关。CARM1 可能是腔型亚分类的潜在标志物,也是靶向治疗的潜在标志物,特别是在 ER 阳性腔型样亚组中。