Epithelial cancer cells are likely to undergo epithelial-mesenchymal transition (EMT) prior to entering the peripheral circulation. By undergoing EMT, circulating tumor cells (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study to investigate mRNA transcripts of EMT-inducing transcription factors (TFs) in tumor cells from the peripheral blood (PB) of patients with primary breast cancer (PBC). PB mononuclear cells were isolated from 52 patients with stages I-III PBC and 30 healthy donors (HDs) and were sequentially depleted of EpCAM + cells and CD45 + leukocytes, henceforth referred to as CD45 -. The expression levels of EMT-inducing TFs (TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2) in the CD45 - cells were determined using quantitative real-time polymerase chain reaction. The highest level of expression by the CD45 - cell fraction of HD was used as "cutoff" to determine if samples from patients with PBC overexpressed any EMT-inducing TFs. In total, 15.4% of patients with PBC overexpressed at least one of the EMT-inducing TF transcripts. Overexpression of any EMT-inducing TF transcripts was more likely to be detected in patients with PBC who received neoadjuvant therapies (NAT) than patients who received no NAT (p = 0.003). Concurrently, CTCs were detected in 7 of 38 (18.4%) patients by CellSearch® and in 15 of 42 (35.7%) patients by AdnaTest™. There was no association between the presence of CTCs measured by CellSearch® or AdnaTest™. In summary, our results demonstrate that CTCs with EMT phenotype may occur in the peripheral circulation of patients with PBC and that NAT is unable to eliminate CTCs undergoing EMT. © 2011 UICC.

Mego, M., Mani, S.A., Lee, B.-., Li, C., Evans, K.W., Cohen, E.N., et al. (2012). Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. INTERNATIONAL JOURNAL OF CANCER, 130(4), 808-816 [10.1002/ijc.26037].

Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy

Giordano A.;
2012-01-01

Abstract

Epithelial cancer cells are likely to undergo epithelial-mesenchymal transition (EMT) prior to entering the peripheral circulation. By undergoing EMT, circulating tumor cells (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study to investigate mRNA transcripts of EMT-inducing transcription factors (TFs) in tumor cells from the peripheral blood (PB) of patients with primary breast cancer (PBC). PB mononuclear cells were isolated from 52 patients with stages I-III PBC and 30 healthy donors (HDs) and were sequentially depleted of EpCAM + cells and CD45 + leukocytes, henceforth referred to as CD45 -. The expression levels of EMT-inducing TFs (TWIST1, SNAIL1, SLUG, ZEB1 and FOXC2) in the CD45 - cells were determined using quantitative real-time polymerase chain reaction. The highest level of expression by the CD45 - cell fraction of HD was used as "cutoff" to determine if samples from patients with PBC overexpressed any EMT-inducing TFs. In total, 15.4% of patients with PBC overexpressed at least one of the EMT-inducing TF transcripts. Overexpression of any EMT-inducing TF transcripts was more likely to be detected in patients with PBC who received neoadjuvant therapies (NAT) than patients who received no NAT (p = 0.003). Concurrently, CTCs were detected in 7 of 38 (18.4%) patients by CellSearch® and in 15 of 42 (35.7%) patients by AdnaTest™. There was no association between the presence of CTCs measured by CellSearch® or AdnaTest™. In summary, our results demonstrate that CTCs with EMT phenotype may occur in the peripheral circulation of patients with PBC and that NAT is unable to eliminate CTCs undergoing EMT. © 2011 UICC.
2012
Mego, M., Mani, S.A., Lee, B.-., Li, C., Evans, K.W., Cohen, E.N., et al. (2012). Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. INTERNATIONAL JOURNAL OF CANCER, 130(4), 808-816 [10.1002/ijc.26037].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1129619
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