Role of claudins 3,4 and 7 in triple negative breast cancer progression

Abstract

Background: Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of cludin 3, claudin 4 and claudin 7 in TNBC promotion and progression. Claudins are tight junction (TJ) integral membrane proteins that are key regulators of the paracellular pathway. Materials and methods: This is a retrospective analysis of 125 patients with triple-negative breast cancer operated at the Institute of Oncology and Radiology of Serbia in the period from 2009 to 2014. The expression of claudin 3, 4 and 7 was observed using the immunohistochemical staining method. The Allred scoring system was used with cut-off values: ≤4 and >4 (low/high expression). Results: Our results showed that the expression of claudins 3 and 4 correlate with higher nuclear gradus and low desease free interval (DFI). More over, the expression of claudin 3 and claudin 4 correlates (Spearman test p˂0.0001). In addition, high expression of claudin 7 is signifi cantly related to low DFI of patients (p˂0.005) and distant metastases. Conclusions: We concluded that claudin 3, claudin 4 and claudin 7 have significant impact on TNBC progression. Namely, elevated expression of these proteins significantly correlates with low DFI and distant metastases. In other words, elevated expression of claudins is a bad news for TNBC patients. Therefore, the expression of claudins could be a good prognostic marker for TNBC patients and potential target for future therapy protocols.