HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer.

Background: Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer...

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Publicado en:Breast Cancer Research Vol. 22; no. 1; pp. 1 - 12
Autores principales: Nanou, Afroditi, Zeune, Leonie Laura, Bidard, Francois-Clement, Pierga, Jean-Yves, Terstappen, Leonardus Wendelinus Mathias Marie
Formato: research Journal Article
Publicado: BioMed Central 8/12/2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 8/12/2020
      vid: 22
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      pub: BioMed Central
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        10.1186/s13058-020-01323-5
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        atl: HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer.
      aug:
        au:
          Nanou, Afroditi
          Zeune, Leonie Laura
          Bidard, Francois-Clement
          Pierga, Jean-Yves
          Terstappen, Leonardus Wendelinus Mathias Marie
        affil: Department of Medical Cell BioPhysics, Faculty of Science and Technology, University of Twente, Carré Room CR4433, Hallenweg 23, 7522 NH, Enschede, The Netherlands
      sug:
        subj:
          Neoplasm Metastasis Metabolism
          Receptors, Cell Surface Metabolism
          Breast Neoplasms Pathology
          Female
          Neoplasm Metastasis
          Breast Neoplasms Metabolism
          Human
          Prognosis
          Breast Neoplasms
          Proteins Metabolism
          ROC Curve
          Survival
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Scales
          Female
      ab: Background: Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients.Methods: Blood samples from 98 patients (CLCC-IC-2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch images using the open-source ACCEPT software.Results: CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2-, CK-HER2+, and CK+HER2+. The inclusion of anti-HER2 increased the percentage of informative samples with ≥ 1 detectable CTC from 89 to 95%. CK- CTCs and tdEVs correlated equally well with the clinical outcome as CK+ CTCs and tdEVs. Inter- and intra-patient heterogeneity was found for the CTC/tdEV phenotypes, and the presence of 2 or 3 classes of CTCs/tdEVs was associated with worse prognosis compared to a uniform CTC/tdEV phenotype present (1 class). The use of ≥ 7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity using the HER2 amplification status of the primary tumor as a classification variable.Conclusions: HER2 can be detected on CTCs and tdEVs not expressing CK, and these CK- CTCs/tdEVs have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the primary tissue. CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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