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.

Keywords: E-cadherin; EGFR; Epithelial-mesenchymal transition (EMT); NF-κB; pathological response; triple-negative breast cancer; tumor marker; vimentin.

Figure 1.

(A) Loss of membranous expression of E-cadherin in this field, which is scored as 3+. (B) Membranous staining of E-cadherin without loss of membranous expression, which is scored as 0.

Figure 2.

(A) No membranous staining for EGFR and (B) some membranous EGFR staining. EGFR indicates epidermal growth factor receptor.

Figure 3.

(A) Negative nuclear staining for NF-κB, regardless of cytoplasmic staining. (B) Nuclear staining of NF-κB. NF-κB indicates nuclear factor κB.

Figure 4.

(A) Negative vimentin staining for tumor cells with positive staining of stromal cells (internal control). (B) Positive cytoplasmic staining for vimentin in tumor cells.