TY - JOUR
T1 - Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer
T2 - The effect of neoadjuvant therapy
AU - Mego, Michal
AU - Mani, Sendurai A.
AU - Lee, Bang Ning
AU - Li, Changping
AU - Evans, Kurt W.
AU - Cohen, Evan N.
AU - Gao, Hui
AU - Jackson, Summer A.
AU - Giordano, Antonio
AU - Hortobagyi, Gabriel N.
AU - Cristofanilli, Massimo
AU - Lucci, Anthony
AU - Reuben, James M.
PY - 2012/2/15
Y1 - 2012/2/15
N2 - 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.
AB - 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.
KW - circulating tumor cells
KW - epithelial-mesenchymal transition
KW - neoadjuvant therapy
KW - primary breast cancer
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U2 - 10.1002/ijc.26037
DO - 10.1002/ijc.26037
M3 - Article
C2 - 21387303
AN - SCOPUS:83955165959
SN - 0020-7136
VL - 130
SP - 808
EP - 816
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -