Expression of epithelial-mesenchymal transition-related markers and phenotypes during breast cancer progression

Abstract

Purpose The study aimed to investigate expression of epithelial-to-mesenchymal transition (EMT)-related proteins and phenotypes during breast cancer progression and to relate this to patient outcome. Methods Protein expression patterns of E-cadherin, N-cadherin, twist, and vimentin were examined by immunohistochemistry on formalin-fixed paraffin-embedded samples from primary tumors (PTs) (n = 419), synchronous lymph node metastases (LNMs) (n = 131) and recurrences (n = 34) from patients included in an observational prospective primary breast cancer study. Markers were evaluated individually and combined as defined EMT phenotypes (epithelial, mesenchymal, partial EMT, and negative). EMT profiles were compared between matched tumor progression stages, and related to clinicopathological data and distant recurrence-free interval (DRFi). Results N-cadherin-positivity, vimentin-positivity, mesenchymal and partial EMT phenotypes were associated with more aggressive tumor characteristics such as triple-negative subtype. Single EMT markers and phenotype discordance rates between paired tumor samples were observed in the range of 2-35%. Non-epithelial phenotypes were more frequently identified in recurrences compared to PTs, however, no skewness of expression or phenotype was detected between PTs and matched LNMs or between PTs and matched recurrences (Exact McNemar test). Interestingly, patients with a twist positive PT had shorter DRFi, compared to patients with a twist negative PT (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.2-5.1, P = 0.02). Essentially, the same effect was seen in multivariable analysis (HR 2.5, 95% CI 0.97-6.6, P = 0.06). Conclusion The epithelial phenotype was indicated to be lost between PTs and recurrences as a reflection of tumor progression. Twist status of the PT was related to long-term prognosis warranting further investigation in larger cohorts.

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

“…This observation was further confirmed at mRNA level, using a clinical cohort of breast tumors. Furthermore, in agreement with our results, vimentin-positive EMT was associated with more aggressive TNBC tumors 41 .…”

Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues

“…The majority (7 cases) were EMT-V (58.3%). This distribution is comparable to a recent tissue microarray immunohistochemical study by Jørgensen et al (2020) 83 where breast cancers which expressed both loss of epithelial and gain of mesenchymal markers (classified as “mesenchymal” in their study and equivalent to EMT-CV in our study) were almost equal in number as those that had absence of both epithelial and mesenchymal markers (classified as “negative” in their study and equivalent to EMT-C in our study). Their study also showed that tumours with retention of epithelial markers but gain of mesenchymal markers (classified as “partial’ in their study and equivalent to EMT-V in our study) was the larger majority.…”

Effect of Invasion of Borrelia burgdorferi in Normal and Neoplastic Mammary Epithelial Cells

“…The results of this study demonstrated a moderate increase in the expression of fibronectin protein in B. burgdorferi infected MCF 10A cells, but there was a detectable increase in the expression level of fibronectin, vimentin, and Twist1/2 protein and a statistically significant increase in activated MMP9 level at 72 h post B. burgdorferi infection in the MDA-MB-231 cells. In good agreement with our findings, a study that investigated the expression of some EMT markers during breast cancer progression also demonstrated vimentin expression positivity associated with aggressive tumors such as the triple-negative subtype [ 37 ]. Similarly, H. pylori significantly upregulates vimentin in the gastric cancer cell lines as well as increases the expression of MMP-7 [ 38 ].…”