Circulating tumour cells in the central and the peripheral venous compartment in patients with metastatic breast cancer

Peeters, Dieter; Eynden, Gert G. Van den; Dam, P Van; Prové, A.; Benoy, Ina; Dam, Peter van; Vermeulen, Peter; Pauwels, Patrick; Peeters, Marc; Laere, Steven J. Van; Dirix, Luc

doi:10.1038/bjc.2011.122

Cited by 27 publications

(23 citation statements)

References 34 publications

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“…Of note, we observed very high numbers of tumor cells of up to 120 per 1 Â 10 6 MNCs in TVB. In the testicular vein, the CTC yield was higher than in peripheral blood, which is similar to the gradients observed in breast and colorectal cancers, where significantly more CTCs could be detected in the central venous blood or the mesenteric vein, respectively (43,44). In more than half of patients with GCTs, clusters of 3 to 7 tumor cells were observed, which was much more frequent than in peripheral blood (20%).…”

Section: Discussionsupporting

confidence: 59%

Circulating Tumor Cells in Patients with Testicular Germ Cell Tumors

Nastały¹,

Ruf

Becker

et al. 2014

Clinical Cancer Research

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Purpose: Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers.Experimental Design: CTCs were enriched from peripheral blood (n ¼ 143 patients) and testicular vein blood (TVB, n ¼ 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system.Results: In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P ¼ 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of a-fetoprotein (AFP; P ¼ 0.025), b-human chorionic gonadotropin (bHCG; P ¼ 0.002), and lactate dehydrogenase (LDH; P ¼ 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood.Conclusions: The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery.

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Section: Discussionsupporting

confidence: 59%

Circulating Tumor Cells in Patients with Testicular Germ Cell Tumors

Nastały¹,

Ruf

Becker

et al. 2014

Clinical Cancer Research

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“…Animal studies indicate that a majority of cancer cells injected intravenously are arrested in the microvasculature of the lungs [42, 44, 45] and that the passage through small capillaries is also tumor dependent [46]. Furthermore, the CTC count has been shown to be higher in the central veins compared to the peripheral veins [47–49]. As an extension of the current study on the effect of breast compression, we intend to draw blood from the superior vena cava in breast cancer patients undergoing preoperative chemotherapy, in addition to peripheral vein sampling, in order to assess the sieving of CTCs in the lung capillaries.…”

Section: Discussionmentioning

confidence: 99%

No evidence for shedding of circulating tumor cells to the peripheral venous blood as a result of mammographic breast compression

Förnvik

Andersson

Dustler

et al. 2013

Breast Cancer Res Treat

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This pilot study aimed to investigate whether mammographic compression procedures might cause shedding of tumor cells into the circulatory system as reflected by circulating tumor cell (CTC) count in peripheral venous blood samples. From March to October 2012, 24 subjects with strong suspicion of breast malignancy were included in the study. Peripheral blood samples were acquired before and after mammography. Enumeration of CTCs in the blood samples was performed using the CellSearch® system. The pressure distribution over the tumor-containing breast was measured using thin pressure sensors. The median age was 66.5 years (range, 51–87 years). In 22 of the 24 subjects, breast cancer was subsequently confirmed. The difference between the average mean tumor pressure 6.8 ± 5.3 kPa (range, 1.0–22.5 kPa) and the average mean breast pressure 3.4 ± 1.6 kPa (range, 1.5–7.1 kPa) was statistically significant (p < 0.001), confirming that there was increased pressure over the tumor. The median pathological tumor size was 19 mm (range, 9–30 mm). Four subjects (17 %) were CTC positive before compression and two of these (8 %) were also CTC positive after compression. A total of seven CTCs were isolated with a mean size of 8 × 6 μm2 (range of the longest diameter, 5–12 μm). The study supports the view that mammography is a safe procedure from the point of view of tumor cell shedding to the peripheral blood.

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“…Consequently, these findings offer a new avenue for understanding human tumor metastasis by interrogating CTCs from multiple vascular sites. Recent studies compared CTC counts among multiple vascular compartments in breast cancer and colorectal cancer, but the clinical relevance of CTC anatomic distribution patterns in HCC still remains unclear (21,31). In this study, we prospectively measured CTCs at five key vascular sites in patients with localized HCC.…”

Section: Discussionmentioning

confidence: 99%

“…The size of CTC was represented as geometrical area of each positive cell, which was calculated according to the following formula: p Â A/2 Â B/2 (A and B represented as the two longest perpendicular diameters measured on screen; ref. 21). Detailed procedures for characterization of EMT-related molecules in CTCs were included in Supplementary Materials.…”

Section: Ctc Enumeration and Characterizationmentioning

confidence: 99%

Circulating Tumor Cells from Different Vascular Sites Exhibit Spatial Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical Significance in Hepatocellular Carcinoma

Sun

Guo

et al. 2018

Clinical Cancer Research

123

126

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Purpose: The spatial heterogeneity of phenotypic and molecular characteristics of CTCs within the circulatory system remains unclear. Herein, we mapped the distribution and characterized biological features of CTCs along the transportation route in hepatocellular carcinoma (HCC).Experimental Design: In 73 localized HCC patients, blood was drawn from peripheral vein (PV), peripheral artery (PA), hepatic veins (HV), infrahepatic inferior vena cava (IHIVC), and portal vein (PoV) before tumor resection. Epithelial and mesenchymal transition (EMT) phenotype in CTCs were analyzed by a 4-channel immunofluorescence CellSearch assay and microfluidic quantitative RT-PCR. The clinical significance of CTCs from different vascular sites was evaluated.Results: The CTC number and size gradient between tumor efferent vessels and postpulmonary peripheral vessels was marked. Tracking the fate of CTC clusters revealed that CTCs displayed an aggregated-singular-aggregated manner of spreading. Single-cell characterization demonstrated that EMT status of CTCs was heterogeneous across different vascular compartments. CTCs were predominantly epithelial at release, but switched to EMT-activated phenotype during hematogeneous transit via Smad2 and b-catenin related signaling pathways. EMT activation in primary tumor correlated with total CTC number at HV, rather than epithelial or EMT-activated subsets of CTCs. Follow-up analysis suggested that CTC and circulating tumor microemboli burden in hepatic veins and peripheral circulation prognosticated postoperative lung metastasis and intrahepatic recurrence, respectively.Conclusions: The current data suggested that a profound spatial heterogeneity in cellular distribution and biological features existed among CTCs during circulation. Multivascular measurement of CTCs could help to reveal novel mechanisms of metastasis and facilitate prediction of postoperative relapse or metastasis pattern in HCC.

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Circulating tumour cells in the central and the peripheral venous compartment in patients with metastatic breast cancer

Cited by 27 publications

References 34 publications

Circulating Tumor Cells in Patients with Testicular Germ Cell Tumors

Circulating Tumor Cells in Patients with Testicular Germ Cell Tumors

No evidence for shedding of circulating tumor cells to the peripheral venous blood as a result of mammographic breast compression

Circulating Tumor Cells from Different Vascular Sites Exhibit Spatial Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical Significance in Hepatocellular Carcinoma

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