Epithelial cell adhesion molecule and epithelial-mesenchymal transition are associated with vasculogenic mimicry, poor prognosis, and metastasis of triple negative breast cancer

Triple-negative breast cancer (TNBC) is associated with epithelial-mesenchymal transition (EMT) and the phenotype of breast cancer stem cells (CSCs). Vasculogenic mimicry (VM) is a novel pattern of tumor blood supply and associated with aggression and metastasis of TNBC. Previous studies have shown that both CSCs and EMT are associated with VM, although the underlying mechanism is yet unclear. The present study aimed to analyze the immunohistochemical (IHC) expression of CSC marker, epithelial cell adhesion molecule (EpCAM), EMT-related markers, including transcription factors (TFs) (Slug, Twist1, and ZEB1), and EMT markers (E-cadherin and vimentin) in 137 TNBC. The expression of these markers was correlated to the clinicopathological features and VM channels of the tumors, including patient overall survival (OS) and disease-free survival (DFS). Furthermore, the expression of EpCAM and EMT-related markers showed a positive correlation with distant metastasis and lymph node metastasis (P < 0.05). A significant association was noted between VM and histological grade (P = 0.007). Moreover, VM showed a significant positive correlation with EpCAM, EMT-associated TFs, and VE-cadherin expression in TNBC. Furthermore, binary logistic analysis showed that VM expression was significantly correlated with lymph node metastasis and distant metastasis (P < 0.05). In survival analysis, the overexpression of EpCAM and ZEB1 predicted a poor prognosis with respect to OS and DFS. In addition, the presence of VM was significantly associated with poor OS and DFS. Multivariate Cox regression analysis revealed that VM expression is an independent prognostic factor for TNBC patients. In summary, VM was confirmed as a potential biomarker for TNBC associated with poor clinical outcomes and tumor metastasis. This study also suggested that EpCAM protein might be involved in VM formation by EMT in TNBC.