Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation

Bilkenroth, Udo; Täubert, Helge; Riemann, Dagmar; Rebmann, U.; Heynemann, H.; Meye, Axel

doi:10.1002/ijc.1217

Cited by 70 publications

(40 citation statements)

References 33 publications

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“…We detected circulating tumor cells in 53% of the renal cell carcinoma patients and in 41% of the peripheral blood samples investigated. In two previous studies where we applied a semi-automated CD45 depletion protocol using an autoMACS, CK+ circulating tumor cells were identified in the peripheral blood of 32% and 42% of renal cell carcinoma patients (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…The mononuclear cells were isolated from 16 mL blood sample obtained by standard Ficoll gradient separation, as described previously (11,12). Briefly, the mononuclear cells were washed once in PBS (containing 2 mmol/L EDTA) and resuspended in 600 μL PBS.…”

Section: Methodsmentioning

confidence: 99%

“…Only the first method allows for the isolation and evaluation of circulating tumor cells by a pathologist. In this study, we did immunomagnetic circulating tumor cell enrichment by depletion of CD45-positive lymphocytes followed by epithelial cell-specific cytokeratin immunocytochemistry, as described previously (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

Bluemke

Bilkenroth

Meye

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Purpose: The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood (so-called circulating tumor cells) for renal cell carcinoma patients. Methods: Two hundred thirty-three peripheral blood samples from 154 renal cell carcinoma patients were investigated for the presence of disseminated tumor cells by autoMACS technique and immunocytochemical staining of cytokeratin. The frequency of circulating tumor cells was analyzed statistically for correlation with relevant clinical data. Results: Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+) and cells without a detectable cytokeratin expression, which we called large blue-stained cells with a tumorlike morphology. After following the CD45 autoMACS depletion protocol, we identified circulating tumor cells in 96 (41%) of 233 peripheral blood samples, which originated from 81 (53%) of 154 renal cell carcinoma patients.A significant correlation between the detection of circulating tumor cells and positive lymph node status (P < 0.001; χ 2 test) and the presence of synchronous metastases at the time of primary tumor resection (P = 0.014; χ 2 test) was found. In a multivariate Cox's regression hazard model, presence of CK+ circulating tumor cells was significantly correlated with poor overall survival for renal cell carcinoma patients (relative risk, 2.3; P = 0.048). Conclusions:The presence of circulating tumor cells correlated to lymph node status and presence of synchronous metastases in renal cell carcinoma. It is important to evaluate CK+ and blue-stained tumor cells together to determine the role of circulating tumor cells in tumor behavior and disease progression. Detection of CK+ circulating tumor cells in peripheral blood is a significant and independent prognostic factor for renal cell carcinoma. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2190-4)

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

Bluemke

Bilkenroth

Meye

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The presence of CTCs in the blood is an obligate step in the spread of solid cancers at distant organs and is thus a major event for its malignant progression. CTCs have been demonstrated in the most common solid malignancies, [1][2][3][4][5][6][7][8][9] and their analysis holds the promise for the better understanding of the key events underlying the progression of this deadly disease. However, there is not yet a comprehensive definition of CTCs based on biological markers.…”

Section: Introductionmentioning

confidence: 99%

Label-free isolation of circulating tumor cells in microfluidic devices: Current research and perspectives

et al. 2013

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This review will cover the recent advances in label-free approaches to isolate and manipulate circulating tumor cells (CTCs). In essence, label-free approaches do not rely on antibodies or biological markers for labeling the cells of interest, but enrich them using the differential physical properties intrinsic to cancer and blood cells. We will discuss technologies that isolate cells based on their biomechanical and electrical properties. Label-free approaches to analyze CTCs have been recently invoked as a valid alternative to "marker-based" techniques, because classical epithelial and tumor markers are lost on some CTC populations and there is no comprehensive phenotypic definition for CTCs. We will highlight the advantages and drawbacks of these technologies and the status on their implementation in the clinics.

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“…However, surgery is associated with considerable perioperative dysfunction of the immune system (Böhm et al, 2001). Also, circulating tumour cells are frequently found in patients with RCC (McKiernan et al, 1999;Ashida et al, 2000;Bilkenroth et al, 2001;Shimazui et al, 2004) and are more prevalent in the renal vein and after surgery (Ashida et al, 2000), possibly owing to surgeryassociated dissemination of tumour cells into the blood circulation, and the presence of circulating tumour cells appears to be associated with a poor prognosis (Shimazui et al, 2004).…”

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confidence: 99%

Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

Klatte

Ittenson

et al. 2006

Br J Cancer

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We conducted a non-randomised controlled phase II trial to investigate the role of preoperative administration of interleukin-2 (IL-2) in patients with renal cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients were allocated alternately to the two study groups: perioperative immunomodulation with IL-2 (IL-2 group; n ¼ 60) and perioperative immunomonitoring without immunomodulation (control group; n ¼ 60). Patients from the IL-2 group received four doses of 10 Â 10 6 IU m À2 twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 Â 10 6 IU m À2 subcutaneously until a day before the operation. Parameters of cellular and humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34, as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist, transforming growth factorb1, and vascular endothelial growth factor) were measured in peripheral venous blood at various intervals. Interleukin-2-related toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period, T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and IL-10 increased. However, all these alterations were significantly less accentuated in patients who had been pretreated with IL-2. Median follow-up was 40 months. Tumour-specific survival in the IL-2 group and the control group was 98 vs 81% after 1 year and 86 vs 73% after 5 years (P ¼ 0.04). A similar effect was found for progression-free survival. We conclude that IL-2 can be safely administered in the perioperative period and modulates immunological parameters. However, to validate the survival data, a larger randomised phase III trial is needed.

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Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation

Cited by 70 publications

References 33 publications

Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Renal Cell Carcinoma Correlates with Prognosis

Label-free isolation of circulating tumor cells in microfluidic devices: Current research and perspectives

Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

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