Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer
Abstract
:1. Introduction
Current presumptions in the adjuvant setting: |
1. Presence of residual disease |
2. Consistent biological characteristics between residual disease and the primary tumor |
3. Consistent treatment sensitivity between residual disease and the primary tumor |
2. Micrometastases
Potential roles for micrometastases: |
1. Refine prognosis |
2. Serial detection to assess efficacy of adjuvant therapy |
3. Biocharacterization of residual disease, with potential therapeutic implications |
3. Detection
3.1. Detection of DTC
3.2. Detection of CTC
Assay System | Enrichment | Detection | Comments |
---|---|---|---|
CellSearch™ | EpCAM antibody coupled ferrofluid | + marker: CK, DAPI | Semiautomated system with FDA approval |
− marker: CD45 | |||
EPISPOT | Depletion of CD45+ cells | Secretion of proteins | Detection of viable epithelial secreting cells |
e.g., CK19; MUC1 | |||
CTC-chip | EpCAM-antibody coated microposts | + marker: CK, DAPI | Captured cells suitable for molecular analysis |
− marker: CD45 | |||
MAINTRAC™ | Red blood cells lysis | + marker: EpCAM | High incidence of positive events. |
− marker: CD45 | |||
Ikoniscope™ | Ficoll or filtration | + marker: EpCAM, CK7/8 | Two epithelial specific Ab and FISH |
FISH: cr 7/8 | |||
Ariol™ | Red blood cells lysis; CK- and EpCAM-antibody coupled microbeads | + marker: CK8/18/19 | Detection of EpCAM+ EpCAM-CTCs |
− marker: CD45 | |||
RT-PCR methods | Immunomagnetic/gradient | Assay specific mRNA | CTC cannot be morphologically identified |
e.g., CK19, HER2, EpCAM |
4. Prognosis
4.1. Prognosis and DTC
4.2. CTC Prognosis
5. Serial Assessment to Monitor Efficacy of Adjuvant Therapy
6. Biocharacterization of Micrometastases
7. Challenges with Micrometastases
7.1. Are These Definitely Cancer Cells?
7.2. Are All Breast Cancer Cells Detected?
7.3. Are DTC and CTC the Same Cells?
7.4. Are These Cells Viable?
8. Long-term
9. Conclusions
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Oakman, C.; Pestrin, M.; Bessi, S.; Galardi, F.; Di Leo, A. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer. Cancers 2010, 2, 1221-1235. https://doi.org/10.3390/cancers2021221
Oakman C, Pestrin M, Bessi S, Galardi F, Di Leo A. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer. Cancers. 2010; 2(2):1221-1235. https://doi.org/10.3390/cancers2021221
Chicago/Turabian StyleOakman, Catherine, Marta Pestrin, Silvia Bessi, Francesca Galardi, and Angelo Di Leo. 2010. "Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer" Cancers 2, no. 2: 1221-1235. https://doi.org/10.3390/cancers2021221