hERG1 channel expression associates with molecular subtypes and prognosis in breast cancer

Jessica Iorio; Icro Meattini; Simonetta Bianchi; Marco Bernini; Virginia Maragna; Luca Dominici; Donato Casella; Vania Vezzosi; Lorenzo Orzalesi; Jacopo Nori; Lorenzo Livi; Annarosa Arcangeli; Elena Lastraioli

doi:10.1186/s12935-018-0592-1

hERG1 channel expression associates with molecular subtypes and prognosis in breast cancer

Cancer Cell Int. 2018 Jul 5:18:93. doi: 10.1186/s12935-018-0592-1. eCollection 2018.

Authors

Affiliations

¹ 1Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Viale GB Morgagni, 50, 50134 Florence, Italy.
² 2Doctorate Course in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy.
³ Radiation Oncology Unit, Department of Oncology, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
⁴ 4Section of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence-Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
⁵ 5Breast Unit Surgery, Department of Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
⁶ Diagnostic Senology Unit, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

Abstract

Background: 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.

Methods: A retrospective pilot study was performed on 40 BC samples by means of immunohistochemistry in order to evaluate hERG1 potassium channels expression in BC.

Results: 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).

Conclusions: 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.

Keywords: Breast cancer; Immunohistochemistry; Molecular subtype; Potassium channels; hERG1.