Frequency and prognostic relevance of disseminated tumor cells in bone marrow of patients with metastatic renal cell carcinoma

Büchner, Alexander; Riesenberg, Rainer; Kotter, Ines; Hofstetter, A.; Stief, Christian G.; Oberneder, R.

doi:10.1002/cncr.21775

Cited by 11 publications

(11 citation statements)

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“…At the follow-up (median, 40 months) 14% of patients with CK+ disseminated tumor cells in their bone marrow suffered from tumor progression in contrast to 11% of patients without CK+ disseminated tumor cells. There is only one report to date, by Buchner and coworkers (20), that shows that detection of disseminated tumor cells in metastatic renal cell carcinoma patients is an independent prognostic factor. They detected CK+ circulating tumor cells in bone marrow samples of 42% of M 1 patients and in 25% of M 0 renal cell carcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, others have reported that the presence of disseminated tumor cells is not convincingly associated with worse survival in operable breast cancer patients (8,18,19). In addition, the prognostic relevance of detection of disseminated tumor cells in the bone marrow of metastatic renal cell carcinoma patients has also been recently shown (20). However, the prognostic impact of circulating tumor cell detection in peripheral blood of renal cell carcinoma patients has not yet been determined.…”

Section: Introductionmentioning

confidence: 97%

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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: Introductionmentioning

confidence: 97%

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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“…Investigations in patients with different tumours have assessed the prognostic value of disseminated epithelial cells in bone marrow and peripheral blood detected by immunocytochemistry using anti-cytokeratin antibodies [46-48]. Only a few studies in RCC patients have demonstrated the possibility of cytokeratin-positive (CK+) cells as markers for CTCs investigated independently in peripheral blood and bone marrow [49,50]. An increase in the number of CK+ cells in RCC patients correlates with advanced tumour stage in RCC [51].…”

Section: Introductionmentioning

confidence: 99%

“…However, in another study, Buchner et al [50] found the prognostic values of disseminated CK+ cells in the bone marrow of patients with metastatic RCC indicated that these cells played an important role in tumour spread in metastatic RCC. The researchers also found that immunocytochemical detection of these cells could be useful in the assessment of clinical outcomes in patients.…”

Section: Introductionmentioning

confidence: 99%

Metastasis-Initiating Cells in Renal Cancer

Khan¹,

Czarnecka²,

Duchnowska³

et al. 2014

CST

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Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of renal cell carcinoma is initiated by circulation of MICs in patients’ blood and bone marrow. Based on the cancer stem/progenitor cell concept of carcinogenesis, understanding the molecular phenotypes of metastasis-initiating cells (MICs) in renal cancer could play a vital role in developing strategies for therapeutic interventions in renal cancer. Existence of MICs among CTCs in renal carcinoma has not been proven in large scale. However, some studies have reported that specialized markers are found on the surface of circulating cells from the primary tumour. In mice, MICs have been isolated from CTCs using such markers, which have then been transplanted into xenograft model to show whether they give rise to metastasis in different organs. Considering these findings, in this review we have attempted to summarize the studies connected with MICs and their gene expression profiles that are responsible for metastasis in renal cancer.

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“…Clear cell RCC (ccRCC) is the most common and the most aggressive subtype of this disease [3]. About one third of the patients already present distant metastases at the time of diagnosis, whereas nearly another third develops metastases during the course of the disease [1, 4]. Although the application of target-directed therapeutics improved the outcome of patients with metastatic ccRCC their prognosis remains unfavourable [5].…”

Section: Introductionmentioning

confidence: 99%

Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis

Fuessel

Erdmann

Täubert³

et al. 2014

BMC Cancer

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BackgroundMembers of the urokinase-type plasminogen activator (uPA) system including uPA, its receptor uPAR and the plasminogen activator inhibitor 1 (PAI-1) play an important role in tumour invasion and progression in a variety of tumour types. Since the majority of clear cell renal cell carcinoma (ccRCC) shows distant metastasis at time of diagnosis or later, the interplay of uPA, uPAR and PAI-1 might be of importance in this process determining the patients’ outcome.MethodsCorresponding pairs of malignant and non-malignant renal tissue specimens were obtained from 112 ccRCC patients without distant metastasis who underwent tumour nephrectomy. Tissue extracts prepared from fresh-frozen tissue samples by detergent extraction were used for the determination of antigen levels of uPA, uPAR and PAI-1 by ELISA. Antigen levels were normalised to protein concentrations and expressed as ng per mg of total protein.ResultsAntigen levels of uPA, uPAR, and PAI-1 correlated with each other in the malignant tissue specimens (rs=0.51-0.65; all P<0.001). Antigen levels of uPA system components were significantly higher in tissue extracts of non-organ confined tumours (pT3+4) compared to organ-confined tumours (pT1+2; all P<0.05). Significantly elevated levels of uPAR and PAI-1 were also observed in high grade ccRCC. When using median antigen levels as cut-off points, all three uPA system factors were significant predictors for disease-specific survival (DSS) in univariate Cox’s regression analyses. High levels of uPA and uPAR remained independent predictors for DSS with HR=2.86 (95% CI 1.07-7.67, P=0.037) and HR=4.70 (95% CI 1.51-14.6, P=0.008), respectively, in multivariate Cox’s regression analyses. A combination of high antigen levels of uPA and/or uPAR further improved the prediction of DSS in multivariate analysis (HR=14.5, 95% CI 1.88-111.1, P=0.010). Moreover, high uPA and/or uPAR levels defined a patient subgroup of high risk for tumour-related death in ccRCC patients with organ-confined disease (pT1+2) (HR=9.83, 95% CI 1.21-79.6, P=0.032).ConclusionsHigh levels of uPA and uPAR in tumour tissue extracts are associated with a significantly shorter DSS of ccRCC patients without distant metastases.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-974) contains supplementary material, which is available to authorized users.

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Frequency and prognostic relevance of disseminated tumor cells in bone marrow of patients with metastatic renal cell carcinoma

Cited by 11 publications

References 54 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

Metastasis-Initiating Cells in Renal Cancer

Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis

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