EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer

Abstract

Circulating tumor cells (CTCs) are frequently associated with epithelialmesenchymal transition (EMT). The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.

Epidermal Growth Factor Receptor Status in Circulating Tumor Cells as a Predictive Biomarker of Sensitivity in Castration-Resistant Prostate Cancer Patients Treated with Docetaxel Chemotherapy

“…Vila et al reported a noticeable positive correlation between the number of EGFR-positive CTCs and worse prognosis, and overall survival in prostate cancer, breast cancer and lung cancer [20]. Serrano et al reported that EGFR-positive CTCs indicate vulnerability to visceral disease [21]. Among our analyzed CRPC blood samples with a CTC count of ≥5 ( n = 37), 40.5% ( n = 15) were positive for EGFR in CTCs.…”

Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility

“…As such, because epithelial cells are rarely present in blood samples from healthy individuals and because circulating epithelial cells (CEC) in patients with cancer often carry the same genetic aberrations seen in the primary tumor (13), the common definition of CTCs has been equivalent to that of CECs: nucleated cells in the bloodstream that express epithelial cytokeratins and do not express the white blood cell surface antigen CD45. More recently, cytokeratin-negative CTCs have been identified, potentially representing tumor cells undergoing epithelial-mesenchymal transition (EMT), or alternatively, cancer stem cells that have not yet shown epithelial differentiation (14)(15)(16)(17).…”

“…Posttreatment ctDNA levels may also be useful in detecting previously unrecognized residual disease following definitive therapy. Anecdotal evidence has been reported to support this concept (7,17,123,124), but large, prospective studies will be needed to demonstrate the prognostic value of residual disease detected by ctDNA. Tie and colleagues (125) have reported preliminary results of a prospective trial in stage II colon cancer evaluating the relationship of postoperative ctDNA levels with tumor recurrence.…”

Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review)

“…When an enrichment of CTCs is done by EpCAM it was recommended, to use a combination of different anti-EpCAM-antibodies, as it was shown, that even different breast cancer cell lines have different EpCAM expression (165). Therefore, it is crucial to regard also EMT-marker genes, as for example lymph node metastases show a strong expression of these genes (166), and a coexpression of EMT-marker genes vIM and Slug is found in patients with CK19-negative CTCs, underlining the importance of focussing on a wider spectrum of marker genes for CTC detection and characterization (167).…”