Expression of Epithelial-mesenchymal Transition-related Markers in Triple-negative Breast Cancer: ZEB1 As a Potential Biomarker for Poor Clinical Outcome

Triple-negative breast cancer (TNBC) is a heterogeneous group of disease with a well-known association with epithelial-mesenchymal transition (EMT) and breast cancer stem cell phenotype. Recent studies have shown that TNBC can be classified into 6 subtypes, including basal-like, mesenchymal-like, and mesenchymal stem-like subtypes. However, clinical significance of the EMT in TNBC remains unclear. We analyzed immunohistochemical expression of EMT-related markers, including EMT markers (expression of vimentin, smooth muscle actin, osteonectin, and N-cadherin; loss of E-cadherin), EMT inducers (ZEB1 and CD146), and breast cancer stem cell markers (CD44(+)/CD24(-) and aldehyde dehydrogenase 1) in 173 TNBCs and correlated their expression with clinicopathological features of the tumors, including clinical outcome. Expressions of vimentin, CD44(+)/CD24(-), and CD146 were more frequent in basal-like TNBCs than non-basal-like TNBCs. Whereas CD146 expression was closely associated with the expression of various EMT markers and CD44(+)/CD24(-) phenotype, ZEB1 expression correlated only with the expression of smooth muscle actin. Expressions of vimentin, smooth muscle actin, osteonectin, and ZEB1 and loss of E-cadherin were more frequently found in metaplastic carcinomas than in other histologic subtypes. In survival analyses, EMT markers were not associated with patients' clinical outcomes. However, ZEB1 expression was found to be an independent prognostic factor for poor disease-free survival. These findings indicate that expression of EMT-related markers in TNBCs can be a signature of a certain subgroup of TNBC, which is associated with metaplastic carcinoma, and ZEB1 expression can serve as a potential biomarker to define a subgroup of TNBC associated with poor clinical outcomes.