Epithelial-Mesenchymal Transition Markers in Breast Cancer and Pathological Responseafter Neoadjuvant Chemotherapy

Abstract

The association between pathologic complete response (pCR) following to neoadjuvant chemotherapy (NAC) and the improved survival in breast cancer has been previously reported. The aim of this study was is to explore the expression of several biomarkers described during epithelial-mesenchymal transition (EMT) and the achievement of pCR in different molecular subtypes of breast cancer. We identified archived pathology tissue from patients with breast cancer who received NAC during the year 2014. We performed immunohistochemical analysis of vimentin, nuclear factor κB (NF-κB), epidermal growth factor receptor (EGFR), E-cadherin, estrogen receptor (ER), progesterone receptor, and Her2neu and studied the association between the expression of these markers and pCR. A Fisher exact test for categorical cofactors, an unpaired t test and a nonparametric Wilcoxon test for continuous cofactors were used. The results showed a significant expression of vimentin in triple-negative breast cancer (TNBC; P = .023). An inverse correlation between vimentin and the ER expression (P = .032) was observed. No significant association was noted for vimentin, NF-κB, EGFR, and E-cadherin was associated with pCR. This study suggests that the evaluated EMT related biomarkers are not associated with pCR after NAC chemotherapy in an unselected breast cancer population. Vimentin and NF-κB expressions were associated with TNBC and could be further explored as potential therapeutic targets in this subgroup. A prevalence of vimentin and NF-κB among Hispanic patients with breast cancer warrants further investigation as a possibly contributing to the prevalence of TNBC and adverse prognosis in this population.

Notch Signaling in Breast Cancer: A Role in Drug Resistance

“…The EMT process is a prerequisite for metastatic spread of the tumor from the primary site (breast) to distant organs (i.e., lymph nodes, bone, brain, lung, or liver). Data suggest that positive regulation of SLUG by Jagged1-mediated activation of Notch IC results in the repression of E-cadherin, thus allowing for EMT in breast cancer cells [ 50 , 51 , 52 ]. Jagged1 overexpression alone is associated with increased bone metastasis, and disruption of the Notch pathway by using the γ-secretase inhibitor (GSI) MRK-003 reversed Jagged-1-mediated bone metastasis in mice [ 53 , 54 ].…”

A “NOTCH” Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer

“…In BC patients, elevated Jagged1 expression and hyperactive Notch signaling has been shown to be predictive of poor prognosis. One study suggests that Jagged1-mediated Notch activation triggers the process of EMT via the repression of E-cadherin by Slug [26,27]. The NICD positively regulates Slug expression by stimulating Slug promoter activation.…”

Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression

“…Another protein implicated in the pro-tumorigenic effects of p62 is Vimentin, a protein involved in tumor progression. Vimentin is a Type III intermediate filament that regulates cell shape, motility, and adhesion during EMT, processes implicated in cell invasion and aggressiveness in cancer cells ( 93 , 94 ). In the highly metastatic MDA-MB-231 breast cancer cell line, vimentin co-immunoprepicitates with endogenous p62.…”