Iorio Jessica, Meattini Icro, Bianchi Simonetta, Bernini Marco, Maragna Virginia, Dominici Luca, Casella Donato, Vezzosi Vania, Orzalesi Lorenzo, Nori Jacopo, Livi Lorenzo, Arcangeli Annarosa, Lastraioli Elena
1Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Viale GB Morgagni, 50, 50134 Florence, Italy.
2Doctorate Course in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy.
Cancer Cell Int. 2018 Jul 5;18:93. doi: 10.1186/s12935-018-0592-1. eCollection 2018.
Breast cancer (BC) is the most frequent malignancy among females worldwide. Despite several efforts and improvements in early diagnosis and treatment, there are still tumors characterized by an aggressive behavior due to unfavorable biology, thus quite difficult to treat. In this view, searching for novel potential biomarkers is mandatory. Among them, in the recent years data have been gathered addressing ion channel as important players in oncology.
A retrospective pilot study was performed on 40 BC samples by means of immunohistochemistry in order to evaluate hERG1 potassium channels expression in BC.
We provide evidence that hERG1 is expressed in all the BC samples analyzed. hERG1 expression was significantly associated with molecular subtype with the highest expression in Luminal A and the lowest in basal-like tumors (p = 0.001), tumor grading (the highest hERG1 expression in well-moderate differentiated tumors, p = 0.020), estrogen receptors (high hERG1 expression in ER-positive samples, p = 0.008) and Ki67 proliferative index (high hERG1 scoring in samples with low proliferative index, p = 0.038). Also, a p value close to significance was noticed for the association between hERG1 and HER2 expression (p = 0.079). At the survival analysis, patients with high hERG1 expression turned out to have a longer progression-free survival, although statistical significance was not reached (p = 0.195). The same trend was observed analyzing local relapse free-survival (LRFS) and metastases-free survival (MFS): patients with higher hERG1 scoring had longer LRFS and MFS (p = 0.124 and p = 0.071, respectively).
The results of this pilot study provide the first evidence that the hERG1 protein is expressed in primary BC, and its expression associates with molecular subtype. hERG1 apparently behaves as a protective factor, since it contributes to identify a subset of patients with better outcome. Overall, these data suggest that hERG1 might be an additional tool for the management of BC, nevertheless further investigations are warranted to better clarify hERG1 role and clinical usefulness in BC.
乳腺癌（BC）是全球女性中最常见的恶性肿瘤。尽管在早期诊断和治疗方面做出了诸多努力并取得了进展，但仍有一些肿瘤因生物学特性不佳而表现出侵袭性，治疗难度较大。因此，寻找新的潜在生物标志物至关重要。其中，近年来已有数据表明离子通道在肿瘤学中起着重要作用。
通过免疫组织化学对40例BC样本进行回顾性初步研究，以评估hERG1钾通道在BC中的表达。
我们提供的证据表明，hERG1在所分析的所有BC样本中均有表达。hERG1表达与分子亚型显著相关，在Luminal A中表达最高，在基底样肿瘤中最低（p = 0.001），与肿瘤分级相关（在高-中分化肿瘤中hERG1表达最高，p = 0.020），与雌激素受体相关（在ER阳性样本中hERG1表达高，p = 0.008）以及与Ki67增殖指数相关（在增殖指数低的样本中hERG1评分高，p = 0.038）。此外，hERG1与HER2表达之间的关联p值接近显著性（p = 0.079）。在生存分析中，hERG1高表达的患者无进展生存期较长，尽管未达到统计学显著性（p = 0.195）。在分析局部无复发生存期（LRFS）和无转移生存期（MFS）时观察到相同趋势：hERG1评分较高的患者LRFS和MFS较长（分别为p = 0.124和p = 0.071）。
这项初步研究的结果首次证明hERG1蛋白在原发性BC中表达，且其表达与分子亚型相关。hERG1显然表现为一种保护因子，因为它有助于识别出预后较好的患者亚组。总体而言，这些数据表明hERG1可能是BC管理的另一种工具，不过仍需进一步研究以更好地阐明hERG1在BC中的作用和临床实用性。
