The Prognostic Impact of the Aryl Hydrocarbon Receptor (AhR) in Primary Breast Cancer Depends on the Lymph Node Status
The Prognostic Impact of the Aryl Hydrocarbon Receptor (AhR) in Primary Breast Cancer Depends on the Lymph Node Status
复制标题
DOI：
10.3390/ijms20051016
复制
发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Cavailles, Vincent
中科院分区：
文献类型：
--
作者：
Jeschke, Udo;Zhang, Xi;Cavailles, Vincent
越来越多的证据表明芳基烃受体（AhR）可能是乳腺癌发生的调节因子。本研究旨在阐明其对乳腺癌（BC）预后的影响。在 mRNA 水平上进行的荟萃分析表明，BC 中 AhR 表达的预测价值取决于淋巴结 (LN) 状态。然后通过免疫组织化学分析 302 个原代 BC 样本中的 AhR 表达和亚细胞定位。 AhR 在几乎 90% 的具有主要核位置的病例中表达。细胞核和细胞质 AhR 水平与 RIP140（140 kDa 的受体相互作用蛋白）、AhR 转录共调节因子和靶基因的表达显着相关。有趣的是，总 AhR 水平和核 AhR 水平仅与淋巴结阴性患者的短期总生存期显着相关。在该亚组中，AhR 总表达和核表达对 RIP140 低表达肿瘤患者的预后影响更大。非常有趣的是，总 AhR 预后值在管腔样 BC 中也很显着，并且是 LN 阴性患者的独立预后标志物。总而言之，这项研究表明 AhR 是 LN 阴性管腔样 BC 患者预后不良的标志，值得进一步评估。
Increasing evidence implicates the aryl hydrocarbon receptor (AhR) as a possible regulator of mammary carcinogenesis. This study aims to clarify its prognostic impact in breast cancer (BC). Meta-analyses performed at the mRNA level demonstrated that the predictive value of AhR expression in BC depends on the lymph node (LN) status. AhR expression and sub-cellular location were then analyzed by immunohistochemistry in 302 primary BC samples. AhR was expressed in almost 90% of cases with a predominant nuclear location. Nuclear and cytoplasmic AhR levels were significantly correlated and associated with the expression of RIP140 (receptor-interacting protein of 140 kDa), an AhR transcriptional coregulator and target gene. Interestingly, total and nuclear AhR levels were only significantly correlated with short overall survival in node-negative patients. In this sub-group, total and nuclear AhR expression had an even stronger prognostic impact in patients with low RIP140-expressing tumors. Very interestingly, the total AhR prognostic value was also significant in luminal-like BCs and was an independent prognostic marker for LN-negative patients. Altogether, this study suggests that AhR is a marker of poor prognosis for patients with LN-negative luminal-like BCs, which warrants further evaluation.