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Cell Cycle Markers in the Evaluation of Bladder Cancer

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Pathology & Oncology Research

Abstract

Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohistochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication.

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References

  1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2014) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase no. 11 [internet]. International Agency for Research on Cancer, Lyon. Available from: http://globocan.iarc.fr. Accessed 22 Apr 2016

  2. Larré S, Catto JWF, Cookson MS, Messing EM, Shariat SF, Soloway MS et al (2013) Screening for bladder cancer: rationale, limitations, whom to target, and perspectives. Eur Urol 63:1049–1058

    Article  Google Scholar 

  3. Kumar V, Abbas AK, Fausto N (2010) Robbins & Cotran pathologic basis of disease, 8th edn. Saunders, Philadelphia

    Google Scholar 

  4. Netto GJ (2012) Molecular biomarkers in urothelial carcinoma of the bladder: are we there yet? Nat Rev Urol 9:41–51

    Article  CAS  Google Scholar 

  5. Parekh DJ, Bochner BH, Dalbagni G (2006) Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments. J Clin Oncol 24:5519–5527

    Article  Google Scholar 

  6. Babjuk M, Burger M, Zigeuner R, Shariat SF, Van Rhijn BWG, Compérat E et al (2013) EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 64:639–653

    Article  Google Scholar 

  7. Goodison S, Rosser CJ, Urquidi V (2013) Bladder cancer detection and monitoring: assessment of urine- and blood-based marker tests. Mol Diagn Ther 17:71–84

    Article  CAS  Google Scholar 

  8. Wang LC, Xylinas E, Kent MT, Kluth LA, Rink M, Jamzadeh A et al (2013) Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder. Urol Oncol 4:433–440

    Google Scholar 

  9. Xylinas E, Kluth LA, Lotan Y, Daneshmand S, Rieken M, Karakiewicz PI et al (2014) Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder. Urol Oncol 32:230–242

    Article  Google Scholar 

  10. Netto GJ, Cheng L (2012) Emerging critical role of molecular testing in diagnostic genitourinary pathology. Arch Pathol Lab Med 136:372–390

    Article  CAS  Google Scholar 

  11. Matsushita K, Cha EK, Matsumoto K, Baba S, Chromecki TF, Fajkovic H et al (2011) Immunohistochemical biomarkers for bladder cancer prognosis. Int J Urol 18:616–629

    CAS  PubMed  Google Scholar 

  12. Kamat AM, Hegartyet RK, Gee JR, Clark PE, Svatek RS, Hegarty N et al (2013) ICUD-EAU international consultation on bladder cancer 2012: screening, diagnosis, and molecular markers. Eur Urol 63:4–15

    Article  Google Scholar 

  13. Cheng L, Davison DD, Adams J, Lopez-Beltran A, Wang L, Montironi R et al (2014) Biomarkers in bladder cancer: translational and clinical implications. Crit Rev Oncol Hemat 89:73–111

    Article  Google Scholar 

  14. Prophet EB, Mills B, Arrington JB et al (1992) Laboratory methods in Histotechnology. Armed forces institute of pathology, Washington, DC

    Google Scholar 

  15. Zavalhia LS, Romitti M, Netto GC, Dos Santos GT, Meurer RT, Hilbig A et al (2012) Evaluation of the expression of C-kit (CD117) in ependymomas and oligodendrogliomas. Dis Markers 33:61–68

    Article  CAS  Google Scholar 

  16. Lotan Y, Bagrodia A, Passoni N, Rachakonda V, Kapur P, Arriaga Y et al (2013) Prospective evaluation of a molecular marker panel for prediction of recurrence and cancer-specific survival after radical cystectomy. Eur Urol 64:465–471

    Article  CAS  Google Scholar 

  17. Olsson H, Hultman P, Monsef N, Rosell J, Jahnson S (2012) Immunohistochemical evaluation of cell cycle regulators: impact on predicting prognosis in stage t1 urinary bladder cancer. ISRN Urol:12:379081

  18. Montironi R, Lopez-Beltran A, Mazzucchelli R, Bostwick DG (2003) Classification and grading of the non-invasive urothelial neoplasms: recent advances and controversies. J Clin Pathol 56:91–95

    Article  CAS  Google Scholar 

  19. Tanagho EA, Mcaninch JW (2010) Urologia Geral de Smith, 17th edn. Porto Alegre, Artmed

    Google Scholar 

  20. Poyet C, Jentsch B, Hermanns T, Schweckendiek D, Seifert H-H, Schmidtpeter M, Sulser T et al (2014) Expression of histone deacetylases 1, 2 and 3 in urothelial bladder cancer. BMC Clin Pathol 14:10

    Article  Google Scholar 

  21. Maeng Y-H, Eun S-Y, Huh J-S (2010) Expression of fibroblast growth factor receptor 3 in the recurrence of non-muscle-invasive urothelial carcinoma of the bladder 2010. Korean J Urol 51:94–100

    Article  Google Scholar 

  22. Wang L, Feng C, Ding G, Ding Q, Zhou Z, Jiang H et al (2014) Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer. Tumor Biol 35:2989–2995

    Article  CAS  Google Scholar 

  23. Rajcani J, Kajo K, Adamkov M, Moravekova LL, Felcanova D et al (2013) Immunohistochemical characterization of urothelial carcinoma. Bratisl Lek Listy 114:431–438

    CAS  PubMed  Google Scholar 

  24. Mitra AP, Bartsch CC, Cote RJ (2009) Strategies for molecular expression profiling in bladder cancer. Cancer Metastasis Rev 28:317–326

    Article  CAS  Google Scholar 

  25. Lee K, Jung ES, Choi Y-J, Lee KY, Lee A (2010) Expression of pRb, p53, p16 and cyclin D1 and their clinical implications in urothelial carcinoma. J Korean Med Sci (10):1449–1455

  26. Krüger S, Mahnken A, Kausch I, Feller AC (2005) P16 Immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma. Eur Urol 47:463–467

    Article  Google Scholar 

  27. Weihong D, Gou Y, Sun C, Xia G, Wang H, Chen Z et al (2014) Ki-67 is an independent indicator in non–muscle invasive bladder cancer (NMIBC); combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC. Urol Oncol-Semin Ori 32:42.e13–42.e19

    Article  Google Scholar 

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Acknowledgements

The authors thank all the staff that works at the Laboratory Research Pathology of Universidade Federal de Ciências da Saúde de Porto Alegre for the generous support in this work.

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Authors and Affiliations

  1. Research Laboratory of Pathology, Health Sciences Federal University of Porto Alegre (UFCSPA), 245 Sarmento Leite, Porto Alegre, RS, 90050-170, Brazil

    Jéssica Niederauer Leote da Silva, Alana Durayski Ranzi, Caroline Trainotti Carvalho, Tales Vicente Scheide, Yuri Thomé Machado Strey, Túlio Meyer Graziottin & Claudia Giuliano Bica

  2. Departament of Urology, Santa Rita Hospital, Hospital system of the Porto Alegre Holy House of Mercy, Porto Alegre, Brazil

    Túlio Meyer Graziottin

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  1. Jéssica Niederauer Leote da Silva
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  2. Alana Durayski Ranzi
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  3. Caroline Trainotti Carvalho
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  4. Tales Vicente Scheide
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  6. Túlio Meyer Graziottin
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  7. Claudia Giuliano Bica
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Correspondence to Claudia Giuliano Bica.

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da Silva, J.N.L., Ranzi, A.D., Carvalho, C.T. et al. Cell Cycle Markers in the Evaluation of Bladder Cancer. Pathol. Oncol. Res. 26, 175–181 (2020). https://doi.org/10.1007/s12253-018-0389-5

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  • DOI: https://doi.org/10.1007/s12253-018-0389-5

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