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International Urology and Nephrology

, Volume 50, Issue 10, pp 1801–1809 | Cite as

Comparison of two detection systems for circulating tumor cells among patients with renal cell carcinoma

  • Menglin Bai
  • Benkui Zou
  • Zhendan Wang
  • Pang Li
  • Huansheng Wang
  • Yang Ou
  • Kai Cui
  • Jiasheng Bian
  • Sheng LiEmail author
  • Xiaobin XuEmail author
Urology - Original Paper
  • 235 Downloads

Abstract

Background/aims

Detection of circulating tumor cells (CTCs) in cancer patients has diagnostic and prognostic importance. However, the clinical implications of CTC detection in patients with renal cell carcinoma (RCC) are still unclear. In this study, we investigated the clinical significance of CTCs using two detection systems, the CellSearch system (CSS) and isolation by size of epithelial tumor cells (ISET), among RCC patients.

Methods

We recruited 36 RCC patients and 22 healthy volunteers as controls. Blood was drawn before treatment. Samples were analyzed using the CSS and ISET. We prospectively followed the RCC patients to determine overall and progression-free survival.

Results

We did not detect CTCs in the control group using either the CSS or ISET. CTCs were detected in 7/36 patients (19.4%) using the CSS and in 13/36 patients (36.1%) using ISET, while circulating microemboli (CTMs) were detected in three patients (8.3%). The presence of ISET-detected CTCs correlated with clinical tumor node metastasis (TNM) stages, while the CSS-detected CTCs did not. After 36 months (median), CTCs detected by both methods failed to correlate with overall and progression-free survival among RCC patients.

Conclusion

We discovered that ISET is more suitable than the CSS for detecting CTCs in RCC patients. The presence of CTCs/CTMs in RCC patients correlated with higher TNM stages, suggesting that the presence of CTCs could be a prognostic marker in RCC patients.

Keywords

Renal cell carcinoma Circulating tumor cell CellSearch Isolation by size of epithelial tumor cell Prognosis 

Notes

Acknowledgements

This study was supported by the project of major innovation and technology sponsored by the Department of Science and Technology of Shandong Province (Grant Number: 2017CXGC1204). Sincere acknowledgements are given to Dr. Zuowei Lu and Dr. Min Liu for assistance with cytopathologic analysis. The authors would also like to thank Wuhan YZY Medical Technological Co. Ltd. and United States Johnson & Johnson Medical Companies for their outstanding technical support.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest to this work.

Ethics approval

This study was approved by the ethical review board of Shandong Cancer Hospital and Institute (approval number: 201405002) and complied with the Helsinki declaration.

Informed consent

Written informed consent was obtained from all participants.

References

  1. 1.
    Chen W, Zheng R, Baade PD et al (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132.  https://doi.org/10.3322/caac.21338 CrossRefPubMedGoogle Scholar
  2. 2.
    Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474CrossRefPubMedGoogle Scholar
  3. 3.
    Gorin MA, Verdone JE, van der Toom E et al (2016) Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer. Nat Rev Urol 14:90–97.  https://doi.org/10.1038/nrurol.2016.224 CrossRefPubMedGoogle Scholar
  4. 4.
    Zhang Y, Lv Y, Niu Y et al (2017) Role of circulating tumor cell (CTC) monitoring in evaluating prognosis of triple-negative breast cancer patients in China. Med Sci Monit 23:3071–3079.  https://doi.org/10.12659/MSM.902637 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Allard WJ, Matera J, Miller MC et al (2005) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904.  https://doi.org/10.1158/1078-0432.CCR-04-0378 CrossRefGoogle Scholar
  6. 6.
    Gradilone A, Iacovelli R, Cortesi E et al (2011) Circulating tumor cells and “suspicious objects” evaluated through CellSearch® in metastatic renal cell carcinoma. Anticancer Res 31:4219–4221PubMedGoogle Scholar
  7. 7.
    Vona G, Sabile A, Louha M et al (2000) Isolation by size of epithelial tumor cells. Am J Pathol 156:57–63.  https://doi.org/10.1016/S0002-9440(10)64706-2 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Farace F, Massard C, Vimond N et al (2011) A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas. Br J Cancer 105:847–853.  https://doi.org/10.1038/bjc.2011.294 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Li H, Song P, Zou B et al (2015) Circulating tumor cell analyses in patients with esophageal squamous cell carcinoma using epithelial marker-dependent and -independent approaches. Medicine (Baltimore) 94:e1565.  https://doi.org/10.1097/MD.0000000000001565 CrossRefGoogle Scholar
  10. 10.
    Khoja L, Backen A, Sloane R et al (2012) A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker. Br J Cancer 106:508–516.  https://doi.org/10.1038/bjc.2011.545 CrossRefPubMedGoogle Scholar
  11. 11.
    Morris KL, Tugwood JD, Khoja L et al (2014) Circulating biomarkers in hepatocellular carcinoma. Cancer Chemother Pharmacol 74:323–332.  https://doi.org/10.1007/s00280-014-2508-7 CrossRefPubMedGoogle Scholar
  12. 12.
    Gutschi T, Pachernegg O, Heidler S et al (2010) Detection of circulating tumor cells in patients with renal cell carcinoma compared with a control group. Eur Urol Suppl 9:649.  https://doi.org/10.1016/S1569-9056(10)61646-6 CrossRefGoogle Scholar
  13. 13.
    Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791.  https://doi.org/10.1056/NEJMoa040766 CrossRefPubMedGoogle Scholar
  14. 14.
    Hofman V, Bonnetaud C, Ilie MI et al (2011) Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker. Clin Cancer Res 17:827–835.  https://doi.org/10.1158/1078-0432.CCR-10-0445 CrossRefPubMedGoogle Scholar
  15. 15.
    Williams SCP (2013) Circulating tumor cells. Proc Natl Acad Sci 110:4861–4861.  https://doi.org/10.1073/pnas.1304186110 CrossRefPubMedGoogle Scholar
  16. 16.
    Gabriel MT, Calleja LR, Chalopin A et al (2016) Circulating tumor cells: a review of non-EpCAM-based approaches for cell enrichment and isolation. Clin Chem 62:571–581CrossRefPubMedGoogle Scholar
  17. 17.
    Ashworth TR (1869) A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 14:146Google Scholar
  18. 18.
    McKiernan JM, Buttyan R, Bander NH, de la Taille A, Stifelman MD, Emanuel ER, Bagiella E, Rubin MA, Katz AE, Olsson CASI (1999) The detection of renal carcinoma cells in the peripheral blood with an enhanced reverse transcriptase-polymerase chain reaction assay for MN/CA9. Cancer 86:492–497CrossRefPubMedGoogle Scholar
  19. 19.
    Shimazui T, Yoshikawa K, Uemura H et al (2003) Detection of cadherin-6 mRNA by nested RT-PCR as a potential marker for circulating cancer cells in renal cell carcinoma. Int J Oncol 23:1049–1054PubMedGoogle Scholar
  20. 20.
    Shimazui T, Yoshikawa K, Uemura H et al (2004) The level of cadherin-6 mRNA in peripheral blood is associated with the site of metastasis and with the subsequent occurrence of metastases in renal cell carcinoma. Cancer 101:963–968.  https://doi.org/10.1002/cncr.20479 CrossRefPubMedGoogle Scholar
  21. 21.
    Gilbert SM, Whitson JM, Mansukhani M et al (2006) Detection of carbonic anhydrase-9 gene expression in peripheral blood cells predicts risk of disease recurrence in patients with renal cortical tumors. Urology 67:942–945.  https://doi.org/10.1016/j.urology.2005.11.034 CrossRefPubMedGoogle Scholar
  22. 22.
    Ming Y, Li Y, Xing H et al (2017) Circulating tumor cells: from theory to nanotechnology-based detection. Front Pharmacol 8:35.  https://doi.org/10.3389/fphar.2017.00035 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Zimpfer A, Maruschke M, Rehn S et al (2014) Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours: a retrospective clinicopathological study of 948 cases using tissue microarrays. BJU Int 114:296–302.  https://doi.org/10.1111/bju.12487 CrossRefPubMedGoogle Scholar
  24. 24.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674.  https://doi.org/10.1016/j.cell.2011.02.013 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol 15:178–196.  https://doi.org/10.1038/nrm3758 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Liu S, Tian Z, Zhang L et al (2016) Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients. Oncotarget 7:1–15.  https://doi.org/10.18632/oncotarget.10979 CrossRefGoogle Scholar
  27. 27.
    Lever E, Sheer D (2010) Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma. J Pathol 220:114–125.  https://doi.org/10.1002/path CrossRefPubMedGoogle Scholar
  28. 28.
    El-Heliebi A, Kroneis T, Zöhrer E et al (2013) Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer? J Transl Med 11:214.  https://doi.org/10.1186/1479-5876-11-214 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Aceto N, Bardia A, Miyamoto DT et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158:1110–1122.  https://doi.org/10.1016/j.cell.2014.07.013 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Fabisiewicz A, Grzybowska E (2017) CTC clusters in cancer progression and metastasis. Med Oncol 34:12.  https://doi.org/10.1007/s12032-016-0875-0 CrossRefPubMedGoogle Scholar
  31. 31.
    Bluemke K, Bilkenroth U, Meye A et al (2009) Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma correlates with prognosis. Cancer Epidemiol Biomark Prev 18:2190–2194.  https://doi.org/10.1158/1055-9965.EPI-08-1178 CrossRefGoogle Scholar
  32. 32.
    Ljungberg B, Bensalah K, Canfield S et al (2015) EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol 67:913–924CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Queen Mary School, Jiangxi Medical CollegeNanchang UniversityNanchangChina
  2. 2.Department of Urological SurgeryShandong Cancer Hospital and InstituteJinanChina
  3. 3.Department of Thoracic SurgeryShandong Cancer Hospital and InstituteJinanChina
  4. 4.Department of Cardiovascular SurgeryGuangzhou Red Cross Hospital Affiliated to Jinan UniversityGuangzhouChina
  5. 5.Department of Hepatobiliary SurgeryShandong Cancer Hospital and InstituteJinanChina
  6. 6.Laboratory of Fear and Anxiety Disorders, Institute of Life ScienceNanchang UniversityNanchangChina

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