LMU Munich, University Hospital, Department of Obstetrics and Gynecology, 81377 Munich, Germany.
Tsinghua Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, China.
Int J Mol Sci. 2019 Feb 26;20(5):1016. doi: 10.3390/ijms20051016.
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.
越来越多的证据表明芳香烃受体（AhR）可能是乳腺癌发生的一个调节因子。本研究旨在阐明其在乳腺癌（BC）中的预后影响。在 mRNA 水平进行的荟萃分析表明，AhR 表达在 BC 中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了 302 例原发性 BC 样本中的 AhR 表达和亚细胞定位。AhR 在近 90%的病例中表达，主要位于核内。核内和细胞质 AhR 水平呈显著相关，并与 AhR 转录共调节剂和靶基因 RIP140 的表达相关。有趣的是，总 AhR 和核 AhR 水平仅与无淋巴结转移患者的总生存期短显著相关。在这个亚组中，总 AhR 和核 AhR 表达在 RIP140 低表达肿瘤患者中的预后影响甚至更强。非常有趣的是，总 AhR 的预后价值在 luminal 样 BC 中也具有统计学意义，是 LN 阴性患者的独立预后标志物。总之，本研究表明 AhR 是 LN 阴性 luminal 样 BC 患者预后不良的标志物，值得进一步评估。
