Biomarkers characterization of circulating tumour cells in breast cancer patients
Nadal Rios, Rosa (Universitat Autònoma de Barcelona. Departament de Medicina)
Fernández González, Ana (Universidad de Granada)
Sanchez-Rovira, Pedro (Universidad de Granada)
Salido, Marta (Hospital del Mar (Barcelona, Catalunya))
Rodríguez, María (Hospital del Mar (Barcelona, Catalunya))
García-Puche, José Luis (Universidad de Granada)
Macià, Marta (Hospital del Mar (Barcelona, Catalunya))
Corominas Torres, Josep M. (Hospital del Mar (Barcelona, Catalunya))
Delgado-Rodríguez, Miguel (Universidad de Jaén)
Gonzalez, Lucas (Universidad de Granada)
Albanell Mestres, Joan (Hospital del Mar (Barcelona, Catalunya))
Fernández, Mónica (Universidad de Granada)
Sole, F (Universitat Autònoma de Barcelona. Departament de Medicina)
Lorente, José Antonio (Universidad de Granada)
Serrano, María José (Universidad de Granada)

Data:	2012
Resum:	Introduction: Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease. Methods: Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics. Results: Baseline detection rate was 46. 9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0. 046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0. 03). Conclusions: This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; Versió publicada
Publicat a:	Breast cancer research, Vol. 14, N. R71 (May 2012) , p. 1-12, ISSN 1465-542X

DOI: 10.1186/bcr3180
PMID: 22554015

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