Vattai Aurelia, Akyol Elif, Kuhn Christina, Hofmann Simone, Heidegger Helene, von Koch Franz, Hermelink Kerstin, Wuerstlein Rachel, Harbeck Nadia, Mayr Doris, Spitzweg Christine, Toth Bettina, Mahner Sven, Jeschke Udo, Ditsch Nina
Department of Gynaecology and Obstetrics, Breast Center, Ludwig-Maximilians University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
Department of Obstetrics and Gynaecology, Klinikum Dritter Orden, Menzinger Str. 44, 80638, Munich, Germany.
J Cancer Res Clin Oncol. 2017 Sep;143(9):1637-1647. doi: 10.1007/s00432-017-2420-8. Epub 2017 Apr 13.
A correlation between breast cancer and thyroid disorders has been described in previous studies. Degraded thyroid hormones are referred to as trace amines. These endogenous amines have the ability to bind to the G-protein-coupled receptor TAAR1 (trace amine-associated receptor) and thereby activate it. TAAR1 is able to modulate the serotonergic and dopaminergic system in the brain and has so far been studied in the neurological field. The following study represents the first investigation of the regulation of TAAR1 in primary breast cancer (no metastases, M0).
Immunohistochemical analyses were carried out to detect TAAR1 expression in formalin fixed paraffin embedded breast cancer samples. Survival times of primary breast cancer patients (M0) with and without TAAR1 expression in their tumours were compared by Kaplan-Meier curves, and correlations between ordinal variables were determined with Spearman's rank correlation coefficient.
The investigation showed a correlation between TAAR1 expression and tumour differentiation grade. A well differentiated tumour grade (G1) was associated with higher TAAR1 expression and HER2 and HER4 positivity predicted higher TAAR1 expression. A TAAR1 overexpression (IRS ≥ 6) was associated with significantly longer overall survival (OS) (p = 0.02) than that of reduced TAAR1 expression (IRS < 6) during a maximum follow-up of 14 years, demonstrating that TAAR1 has a favourable effect on OS of early breast cancer patients.
We conclude that TAAR1 seems to be an independent predictor for breast cancer survival. Modulation of TAAR1 may represent a novel targeting strategy for breast cancer prevention and therapy.
先前的研究已描述了乳腺癌与甲状腺疾病之间的关联。降解的甲状腺激素被称为痕量胺。这些内源性胺能够与G蛋白偶联受体TAAR1（痕量胺相关受体）结合，从而激活它。TAAR1能够调节大脑中的血清素能和多巴胺能系统，迄今为止已在神经学领域进行了研究。以下研究是对原发性乳腺癌（无转移，M0）中TAAR1调节的首次调查。
进行免疫组织化学分析以检测福尔马林固定石蜡包埋的乳腺癌样本中TAAR1的表达。通过Kaplan-Meier曲线比较原发性乳腺癌患者（M0）肿瘤中有或无TAAR1表达的生存时间，并用Spearman等级相关系数确定有序变量之间的相关性。
研究表明TAAR1表达与肿瘤分化程度之间存在相关性。高分化肿瘤分级（G1）与较高的TAAR1表达相关，HER2和HER4阳性预示着较高的TAAR1表达。在最长14年的随访期间，TAAR1过表达（免疫反应性评分≥6）与总生存期（OS）显著延长（p = 0.02）相关，而TAAR1表达降低（免疫反应性评分<6）的患者则不然，这表明TAAR1对早期乳腺癌患者OS有有利影响。
我们得出结论，TAAR1似乎是乳腺癌生存的独立预测因子。调节TAAR1可能代表一种预防和治疗乳腺癌的新靶向策略。
