Detection of circulating tumor cells and their potential use as a biomarker for advanced renal cell carcinoma

  • Tae Heon Kim
  • Yoon-Tae Kang
  • Young-Ho Cho
  • Jeong Hoon Kim
  • Byong Chang Jeong
  • Seong Il Seo
  • Seong Soo Jeon
  • Hyun Moo Lee
Keywords: circulating tumor cells, renal cell carcinoma, biomarker, survival, tapered-slit filter

Abstract

Introduction: The aim of this study was to detect circulating tumor cells (CTCs) in patients with advanced renal cell carcinoma (RCC) using a novel CTC detection platform. Furthermore, we evaluated the clinical outcomes associated with a CTC-positive status.

Methods: A total of 34 patients with advanced RCC (stage III or IV) were prospectively enrolled, and 104 peripheral blood samples were analyzed for the presence of CTCs at various time points. CTCs were isolated using a tapered-slit filter, which captures CTCs based on size and deformability. The presence of CTCs was confirmed using both staining and morphological criteria. CTC status was then correlated with clinical characteristics and survival outcomes.

Results: CTCs were detected in 62% of patients during the pretreatment period, and the median CTC count was 2 (interquartile range 1–3). During the followup period, CTCs were detected in 56% (18/32), 65% (20/31), and 41% (7/17) of patients at one week, one month, and three months after treatment, respectively. Overall, CTCs were found in 57.9% (66/114) of blood samples in the range of 1–7 cells. Although no statistical significance was found, CTC detection in patients with stage IV disease was more common than in patients with stage III disease (68.4% vs. 53.3%). Two-year progression-free survival and cancer-specific survival tended to be lower in CTCpositive patients compared with CTC-negative patients.

Conclusions: The tapered-slit filter is an efficient technique to detect CTCs in advanced RCC.

References

Ljungberg B, Campbell SC, Choi HY, et al. The epidemiology of renal cell carcinoma. Eur Urol. 2011;60:615-21.

Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359-86.

Jung KW, Won YJ, Oh CM, et al. Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2014. Cancer Res Treat. 2017;49:292-305.

Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781-91.

de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14:6302-09.

Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:3213-21.

Bluemke K, Bilkenroth U, Meye A, et al. Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis. Cancer Epidemiol Biomarkers Prev. 2009;18:2190-94.

Tan KV, Namdarian B, Costello AJ, et al. Potential use of circulating endothelial cells as a biomarker of renal cell carcinoma. Urol Oncol. 2011;29:237-43.

Small AC, Gong Y, Oh WK, et al. The emerging role of circulating tumor cell detection in genitourinary cancer. J Urol. 2012;188:21-6.

Kang YT, Doh I, Cho YH. Tapered-slit membrane filters for high-throughput viable circulating tumor cell isolation. Biomed Microdevices. 2015;17:45.

Paner GP, Stadler WM, Hansel DE, et al. Updates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers. Eur Urol. 2018;73:560-9.

Kang YT, Doh I, Byun J, et al. Label-free Rapid Viable Enrichment of Circulating Tumor Cell by Photosensitive Polymer-based Microfilter Device. Theranostics. 2017;7:3179-91.

Bhatt RS, Zurita AJ, O'Neill A, et al. Increased mobilisation of circulating endothelial progenitors in von Hippel-Lindau disease and renal cell carcinoma. Br J Cancer. 2011;105:112-7.

Gruenwald V, Beutel G, Schuch-Jantsch S, et al. Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib. BMC Cancer. 2010;10:695.

Ko JS, Zea AH, Rini BI, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15:2148-57.

Kusmartsev S, Su Z, Heiser A, et al. Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2008;14:8270-8.

Hernandez-Yanez M, Heymach JV, Zurita AJ. Circulating biomarkers in advanced renal cell carcinoma: clinical applications. Curr Oncol Rep. 2012;14:221-9.

McKiernan JM, Buttyan R, Bander NH, et al. The detection of renal carcinoma cells in the peripheral blood with an enhanced reverse transcriptase-polymerase chain reaction assay for MN/CA9. Cancer. 1999;86:492-7.

Shimazui T, Yoshikawa K, Uemura H, et al. Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma. Int J Oncol. 2003;23:1049-54.

Li G, Passebosc-Faure K, Gentil-Perret A, et al. Cadherin-6 gene expression in conventional renal cell carcinoma: a useful marker to detect circulating tumor cells. Anticancer Res. 2005;25:377-81.

Bilkenroth U, Taubert H, Riemann D, et al. Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation. Int J Cancer. 2001;92:577-82.

Blumke K, Bilkenroth U, Schmidt U, et al. Detection of circulating tumor cells from renal carcinoma patients: experiences of a two-center study. Oncol Rep. 2005;14:895-9.

Gradilone A, Iacovelli R, Cortesi E, et al. Circulating tumor cells and "suspicious objects" evaluated through CellSearch(R) in metastatic renal cell carcinoma. Anticancer Res. 2011;31:4219-21.

Giordano A, Gao H, Anfossi S, et al. Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther. 2012;11:2526-34.

Tiwari A, Punshon G, Kidane A, et al. Magnetic beads (Dynabead) toxicity to endothelial cells at high bead concentration: implication for tissue engineering of vascular prosthesis. Cell Biol Toxicol. 2003;19:265-72.

Shen Q, Xu L, Zhao L, et al. Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates. Adv Mater. 2013;25:2368-73.

Huang T, Jia CP, Jun Y, et al. Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip. Biosens Bioelectron. 2014;51:213-8.

Farace F, Massard C, Vimond N, et al. A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas. Br J Cancer. 2011;105:847-53.

Adams DL, Stefansson S, Haudenschild C, et al. Cytometric characterization of circulating tumor cells captured by microfiltration and their correlation to the CellSearch((R)) CTC test. Cytometry A. 2015;87:137-44.

Suh DH, Kim M, Choi JY, et al. Circulating tumor cells in the differential diagnosis of adnexal masses. Oncotarget. 2017;8:77195-206.

Published
2018-11-27
How to Cite
Kim, T. H., Kang, Y.-T., Cho, Y.-H., Kim, J. H., Jeong, B. C., Seo, S. I., Jeon, S. S., & Lee, H. M. (2018). Detection of circulating tumor cells and their potential use as a biomarker for advanced renal cell carcinoma. Canadian Urological Association Journal, 13(9). Retrieved from https://cuaj.ca/index.php/journal/article/view/5605
Section
Original Research