Research Papers:

Phenotypic characterization of circulating tumor cells in triple negative breast cancer patients

Sofia Agelaki, Melina Dragolia, Harris Markonanolaki, Saad Alkahtani, Christos Stournaras, Vassilis Georgoulias and Galatea Kallergi _

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Oncotarget. 2017; 8:5309-5322. https://doi.org/10.18632/oncotarget.14144

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Sofia Agelaki1,2, Melina Dragolia3, Harris Markonanolaki3, Saad Alkahtani4,5, Christos Stournaras5, Vassilis Georgoulias3, Galatea Kallergi3,5

1Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, Heraklion, Greece

2Department of Medical Oncology, University General Hospital of Heraklion, Voutes, Heraklion, Greece

3Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Voutes, Heraklion, Greece

4Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia

5Department of Biochemistry, University of Crete Medical School, Voutes, Heraklion, Greece

Correspondence to:

Galatea Kallergi, email: [email protected]

Keywords: CTCs, HER2, estrogen receptor, progesteron receptor, EGFR

Received: August 01, 2016     Accepted: November 22, 2016     Published: December 24, 2016


Introduction: Patients with triple negative breast cancer (TNBC), are considered as a poor prognosis group for whom no targeted therapies are currently available. The aim of the present study was to phenotypically characterize their CTCs in order to explore potential therapeutic targets.

Methods: PBMC’s cytospins were prepared from 45 early (before and after adjuvant chemotherapy), 10 metastatic TNBC and 21 hormone receptor (HR) -positive patients. The expression of Cytokeratins (CK), ER, PR, EGFR and HER2 on CTCs was assessed using immunofluoresence staining and ARIOL analysis.

Results: In early stage TNBC, ER, PR, HER2 and EGFR expressing-CTCs were detected in 24.4%, 24.4%, 20% and 40% of patients before the initiation of adjuvant chemotherapy, and in 17.8%, 13.3% 6.7% and 51.1% respectively after the completion of adjuvant treatment. Triple staining experiments revealed distinct subpopulations of CTC expressed HR, and ErbB family receptors. In patients with metastatic disease, the frequency of HER2+ CTCs was significantly increased compared to adjuvant setting (60% vs 20%, p=0.014). The presence of CK+PR- CTCs, before adjuvant treatment was associated with reduced OS (p=0.032) and DFI (p=0.04). Furthermore, the frequency of ER-, PR- and HER2+ CTCs was higher in HR(+) than in TNBC tumors (57.1%, p=0.006; 52.4%, p=0.021 and 52.38%, p=0.009, respectively).

Conclusions: The CTCs in patients with early TNBC are phenotypically heterogeneous based on the expression of HR, EGFR and HER2 both before and after the completion of adjuvant chemotherapy whereas the presence of HER2+ CTCs prevails during disease evolution. These findings could be of clinical relevance in terms of CTC targeting.

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