Abstract
Objectives
Long-term follow-up study to evaluate the impact on disease-free survival and cancer-specific survival of survivin expression in tissue and CTCs from T1G3 bladder cancer patients.
Patients and methods
The study was conducted using tumor tissue and blood samples from 54 patients with a primary diagnosis of T1G3 NMIBC. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumor tissues. CTCs were isolated from blood by CELLection™ Dynabeads (Invitrogen, Carlsbad, CA, USA). Cells were lysed and cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The endpoints of this long-termanalysis were disease-free survival, DFS and cancer-specific survival, CSS.
Results
Here, we report that, at 9 years of median follow-up, disease-free survival and cancer-specific survival are both significantly influenced by the expression of survivin in tumor tissue (p = 0.006), by the presence of CTCs (p < 0.0001) and by the expression of survivin in CTCs (p < 0.0001).
Conclusion
The statistically significant impact of survivin expressing CTCs on cancer-specific survival that we observed might be interpreted as the result of the persistence of a subpopulation of highlander cells in the blood of T1G3 bladder patients over time.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- CSS:
-
Cancer-specific survival
- CTCs:
-
Circulating tumor cells
- DFS:
-
Disease-free survival
- IAP:
-
Inhibitor of apoptosis
- NMIBC:
-
Non-muscle invasive bladder cancer
- PPV:
-
Positive predictive value
- TFR:
-
Time to first recurrence
- TTP:
-
Time to progression
References
Alix-Panabières C, Pantel K (2016) Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 6(5):479–491
Birkenkamp-Demtröder K, Nordentoft I, Christensen E et al (2016) Genomic alterations in liquid biopsies from patients with bladder cancer. Eur Urol 70(1):75–82
Bolenz C, Lotan Y (2010) Translational research in bladder cancer: from molecular pathogenesis to useful tissue biomarkers. Cancer Biol Ther 10(5):407–415
Burger M, Catto JW, Dalbagni G et al (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63(2):234–241
De Berardinis E, Busetto GM, Antonini G, Giovannone R, Gentile V (2011) T1G3 high-risk NMIBC (non-muscle invasive bladder cancer): conservative treatment versus immediate cystectomy. Int Urol Nephrol 43(4):1047–1057
Garg H, Suri P, Gupta JC, Talwar GP, Dubey S (2016) Survivin: a unique target for tumor therapy. Cancer Cell Int 16:49
Gazzaniga P, de Berardinis E, Raimondi C et al (2014) Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer. Int J Cancer 135(8):1978–1982
Gradilone A, Petracca A, Nicolazzo C et al (2010) Prognostic significance of survivin-expressing circulating tumour cells in T1G3 bladder cancer. BJU Int 106(5):710–715
Kang M, Ku JH (2016) Liquid biopsy? A recent breakthrough in noninvasive bladder cancer surveillance. Investig Clin Urol 57(5):307–308
Kim K, Sung CO, Park BH et al (2015) Immunoprofile-based subgrouping of urothelial bladder carcinomas for survival prediction. Hum Pathol 46(10):1464–1470
Kluth LA, Black PC, Bochner BH et al (2015) Prognostic and prediction tools in bladder cancer: a comprehensive review of the literature. Eur Urol 68(2):238–253
Knowles MA, Hurst CD (2015) Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer 15(1):25–41
Mobahat M, Narendran A, Riabowol K (2014) Survivin as a preferential target for cancer therapy. Int J Mol Sci 15(2):2494–2516
Noman MZ, Messai Y, Muret J, Hasmim M, Chouaib S (2014) Crosstalk between CTC, immune system and hypoxic tumor microenvironment. Cancer Microenviron 7(3):153–160
Sanguedolce F, Cormio A, Bufo P, Carrieri G, Cormio L (2015) Molecular markers in bladder cancer: novel research frontiers. Crit Rev Clin Lab Sci 52(5):242–255
Soave A, Riethdorf S, Pantel K, Fisch M, Rink M (2015) Do circulating tumor cells have a role in deciding on adjuvant chemotherapy after radical cystectomy? Curr Urol Rep 16(7):46
Soave A, Riethdorf S, Dahlem R et al (2017) A nonrandomized, prospective, clinical study on the impact of circulating tumor cells on outcomes of urothelial carcinoma of the bladder patients treated with radical cystectomy with or without adjuvant chemotherapy. Int J Cancer 140(2):381–389
Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) Predicting recurrence and progression in individual patients with stage Ta, T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49(3):466–477
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declared that they have no competing interest.
Funding
Nothing to declare.
Ethical approval
All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Nicolazzo, C., Busetto, G.M., Del Giudice, F. et al. The long-term prognostic value of survivin expressing circulating tumor cells in patients with high-risk non-muscle invasive bladder cancer (NMIBC). J Cancer Res Clin Oncol 143, 1971–1976 (2017). https://doi.org/10.1007/s00432-017-2449-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-017-2449-8