Epithelial–Mesenchymal Transitioned Circulating Tumor Cells Capture for Detecting Tumor Progression

Background: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. Methods: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). Results: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p < 0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. Conclusions: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy.

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Tyrosinase mRNA levels in the blood of uveal melanoma patients: correlation with the number of circulating tumor cells and tumor progression

Melanoma Research ◽

10.1097/cmr.0b013e32833906e3 ◽

2010 ◽

Vol 20 (4) ◽

pp. 303-310 ◽

Cited By ~ 20

Author(s):

Pamela Pinzani ◽

Cinzia Mazzini ◽

Francesca Salvianti ◽

Daniela Massi ◽

Raffaella Grifoni ◽

...

Keyword(s):

Tumor Progression ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Uveal Melanoma ◽

Mrna Levels ◽

Melanoma Patients

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MicroRNA for circulating tumor cells detection in breast cancer: In silico and in vitro analysis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22027 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22027-e22027 ◽

Cited By ~ 1

Author(s):

V. Medina Villaamil ◽

M. Blanco Calvo ◽

S. M. Díaz Prado ◽

S. Antolín Novoa ◽

L. Calvo Martínez ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Progression ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cell Lines ◽

In Silico ◽

Detection Methods ◽

Computational Tools ◽

Relative Expression ◽

Qrt Pcr

e22027 Background: Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in breast cancer (bc) patients. Deregulation of microRNAs (miRNAs) is frequent in tumors, including breast cancer. It is suggested miRNAs play a role in tumor progression. We hypothesized that miRNAs may constitute a promising new class of cancer biomarkers for CTC detection. Our objective has been to identify miRNAs potentially useful for CTC detection. Methods: Phase I preclinical study was performed by means of computational tools for miRNAs profiling including MIRGATOR, MIRBASE, SMIRNAdb, GeneHUB-GEPIS, MICRORNA.ORG, and MIRNAMAP. In silico data were used to identify and prioritize miRNAs highly expressed in breast cancer, but absent in hematopoietic-derived sources. Selected miRNAs were evaluated by means of qRT-PCR in breast cancer and Hematopoietic cell lines, normal blood, and blood from breast cancer patients. Results: Computational tools identify a set of miRNAs highly expressed in breast cancer sources in relation to hematopoietic samples. Among these were miR-141, miR-200c, miR-196a, miR-203, miR-200a, miR-200b, miR-32, miR-375, miR-31, miR-193a, and miR-205. For instance, relative expression of miR-32 was 104 higher in bc cell lines (N= 5) than in normal PB (N = 19) using qRT-PCR. In a preliminary analysis of PB from bc patients (stage IV) higher relative expression levels for selected miRNAs were found comparing with age-matched controls’ blood. Conclusions: Our results suggest that miRNA bioinformatic approach is a useful high-throughput method to select bc-associated miRNAS. The selected miRNAs should be further evaluated for their potential as markers for CTC detection. We next investigate if blood miRNA profile could predict tumor progression and survival. Supported by grants PI06/1541 and PI07/0477 from Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III. No significant financial relationships to disclose.

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