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

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.

• Authors: Michal Mego, Sendurai A Mani, Bang-Ning Lee, Changping Li, Kurt W Evans, Evan N Cohen, Hui Gao, Summer A Jackson, Antonio Giordano, Gabriel N Hortobagyi, Massimo Cristofanilli, Anthony Lucci, James M Reuben
• Journal: International journal of cancer (Int J Cancer) Vol. 130 Issue 4 Pg. 808-16 (Feb 15 2012) ISSN: 1097-0215 [Electronic] United States
• PMID: 21387303 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2011 UICC.

Chemical References

• Forkhead Transcription Factors
• Homeodomain Proteins
• Nuclear Proteins
• RNA, Messenger
• SNAI1 protein, human
• Snail Family Transcription Factors
• TWIST1 protein, human
• Transcription Factors
• Twist-Related Protein 1
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• mesenchyme fork head 1 protein
• Leukocyte Common Antigens
• PTPRC protein, human

Topics

• Breast Neoplasms (metabolism, pathology, therapy)
• Epithelial-Mesenchymal Transition
• Female
• Forkhead Transcription Factors (genetics)
• Homeodomain Proteins (genetics)
• Humans
• Leukocyte Common Antigens (analysis)
• Neoadjuvant Therapy
• Neoplastic Cells, Circulating
• Nuclear Proteins (genetics)
• RNA, Messenger (analysis)
• Snail Family Transcription Factors
• Transcription Factors (genetics)
• Twist-Related Protein 1 (genetics)
• Zinc Finger E-box-Binding Homeobox 1