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Disease Markers
Volume 2016, Article ID 5259602, 13 pages
http://dx.doi.org/10.1155/2016/5259602
Review Article

Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis

1Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China
2Department of Children Rehabilitation Medicine, Guangxi Maternal and Child Health Hospital, 225 Xinyang Road, Nanning, Guangxi Zhuang Autonomous Region 530003, China
3Center of Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China

Received 15 September 2015; Accepted 27 March 2016

Academic Editor: Ja Hyeon Ku

Copyright © 2016 Xiaoning Gan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Ploeg, K. K. H. Aben, and L. A. Kiemeney, “The present and future burden of urinary bladder cancer in the world,” World Journal of Urology, vol. 27, no. 3, pp. 289–293, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. D. S. Kaufman, W. U. Shipley, and A. S. Feldman, “Bladder cancer,” The Lancet, vol. 374, no. 9685, pp. 239–249, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Serrano, G. J. Hannon, and D. Beach, “A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4,” Nature, vol. 366, no. 6456, pp. 704–707, 1993. View at Publisher · View at Google Scholar · View at Scopus
  4. I. Orlow, H. LaRue, I. Osman et al., “Deletions of the INK4A gene in superficial bladder tumors. Association with recurrence,” The American Journal of Pathology, vol. 155, no. 1, pp. 105–113, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Krüger, A. Mahnken, I. Kausch, and A. C. Feller, “P16 immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma,” European Urology, vol. 47, no. 4, pp. 463–467, 2005. View at Publisher · View at Google Scholar · View at Scopus
  6. A. O. Yurakh, D. Ramos, S. Calabuig-Fariñas et al., “Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder,” European Urology, vol. 50, no. 3, pp. 506–515, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. A. P. Mitra, D. E. Hansel, and R. J. Cote, “Prognostic value of cell-cycle regulation biomarkers in bladder cancer,” Seminars in Oncology, vol. 39, no. 5, pp. 524–533, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Bartoletti, T. Cai, G. Nesi, L. Roberta Girardi, G. Baroni, and M. Dal Canto, “Loss of P16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer,” Journal of Surgical Research, vol. 143, no. 2, pp. 422–427, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Chakravarti, K. Winter, C.-L. Wu et al., “Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group,” International Journal of Radiation Oncology Biology Physics, vol. 62, no. 2, pp. 309–317, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. A. W. Hitchings, M. Kumar, S. Jordan, V. Nargund, J. Martin, and D. M. Berney, “Prediction of progression in pTa and pTl bladder carcinomas with p53, p16 and pRb,” British Journal of Cancer, vol. 91, no. 3, pp. 552–557, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. K. Lee, E. S. Jung, Y.-J. Choi, K. Y. Lee, and A. Lee, “Expression of pRb, p53, p16 and cyclin D1 and their clinical implications in urothelial carcinoma,” Journal of Korean Medical Science, vol. 25, no. 10, pp. 1449–1455, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Mhawech, V. Greloz, C. Oppikofer, I. Szalay-Quinodoz, and F. Herrmann, “Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and their value in predicting tumor progression,” Cancer, vol. 100, no. 11, pp. 2367–2375, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. C.-C. Yang, K.-C. Chu, H.-Y. Chen, and W.-C. Chen, “Expression of p16 and cyclin D1 in bladder cancer and correlation in cancer progression,” Urologia Internationalis, vol. 69, no. 3, pp. 190–194, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Brunner, I. Verdorfer, M. Prelog, C. Mayerl, G. Mikuz, and A. Tzankov, “Large-scale analysis of cell cycle regulators in urothelial bladder cancer identifies p16 and p27 as potentially useful prognostic markers,” Pathobiology, vol. 75, no. 1, pp. 25–33, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. M. G. Friedrich, C. Blind, K. Milde-Langosch et al., “Frequent p16/MTS1 inactivation in early stages of urothelial carcinoma of the bladder is not associated with tumor recurrence,” European Urology, vol. 40, no. 5, pp. 518–524, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Korkolopoulou, P. Christodoulou, A. Lazaris et al., “Prognostic implications of aberrations in p16/pRb pathway in urothelial bladder carcinomas: a multivariate analysis including p53 expression and proliferation markers,” European Urology, vol. 39, no. 2, pp. 167–177, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. G. A. Niehans, R. A. Kratzke, M. K. Froberg, D. M. Aeppli, P. L. Nguyen, and J. Geradts, “G1 checkpoint protein and p53 abnormalities occur in most invasive transitional cell carcinomas of the urinary bladder,” British Journal of Cancer, vol. 80, no. 8, pp. 1175–1184, 1999. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Røtterud, E. O. Pettersen, A. Berner, R. Holm, D. R. Olsen, and S. D. Fosså, “Cell cycle inhibitors and outcome after radiotherapy in bladder cancer patients,” Acta Oncologica, vol. 41, no. 5, pp. 463–470, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. F. R. Vallmanya Llena, A. Laborda Rodríguez, J. Lloreta Trull, R. Cortadella Ángel, J. Placer Santos, and A. Gelabert Mas, “Immunohistochemical expression of p53, p21, p16, and cyclin D1 in superficial bladder cancer. A tissue microarray study,” Actas Urologicas Espanolas, vol. 30, no. 8, pp. 754–762, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Sun, Z. W. Chen, S. M. Zhang, and T. R. Ma, “Expression of tumor suppressor gene Rb, MTS1 and prognosis of bladder cancer,” Chinese Journal of Clinical Oncology, vol. 27, pp. 177–179, 2000. View at Google Scholar
  21. L. L. Santos, T. Amaro, S. A. Pereira et al., “Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder,” European Journal of Surgical Oncology, vol. 29, no. 1, pp. 74–80, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Yin, S. Bastacky, A. V. Parwani, T. McHale, and R. Dhir, “p16ink4 immunoreactivity is a reliable marker for urothelial carcinoma in situ,” Human Pathology, vol. 39, no. 4, pp. 527–535, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Primdahl, H. Von der Maase, F. B. Sørensen, H. Wolf, and T. F. Ørntoft, “Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer,” Journal of Cancer Research and Clinical Oncology, vol. 128, no. 6, pp. 295–301, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. J. O. Jin, J. Lehmann, J. Taxy et al., “Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in patients with locally advanced bladder cancer,” Clinical Genitourinary Cancer, vol. 5, no. 2, pp. 150–154, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. T.-S. Tzai, Y.-S. Tsai, and N.-H. Chow, “The prevalence and clinicopathologic correlate of p16INK4a, retinoblastoma and p53 immunoreactivity in locally advanced urinary bladder cancer,” Urologic Oncology: Seminars and Original Investigations, vol. 22, no. 2, pp. 112–118, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. T. X. Jin, W. Y. Wu, X. G. Li, and D. M. Piao, “Expression and significance of cyclinD1, PCNA and p16 in transitional cellcarcinoma of the bladder,” Journal of Medical Science Yanbian University, vol. 27, pp. 279–282, 2004 (Chinese). View at Google Scholar
  27. Z. Q. Fu and W. Li, “The expression and significance of E-CD and p16 in transitional cell carcinoma of bladder,” Chinese Journal of Experimental Surgery, vol. 28, pp. 284–285, 2011 (Chinese). View at Google Scholar
  28. H. L. Shi, R. J. Zhou, J. Y. Cheng et al., “Expression and significance of p16 and PCNA in bladder transitional cell carcinoma,” Shandong Medical Journal, vol. 41, pp. 12–14, 2001 (Chinese). View at Google Scholar
  29. H. W. Wang, “Expression of p16 gene in carcinoma of bladder and cystitis glandularis,” Modern Practical Medicine, vol. 13, pp. 169–170, 2001 (Chinese). View at Google Scholar
  30. S. M. Miao, “p16 and cyclin D1 gene expressions in bladder transition cell carcinoma,” Chinese Journal of Urology, vol. 20, pp. 419–421, 1999 (Chinese). View at Google Scholar
  31. H. Q. Shi, S. X. Lou, and Q. W. Liu, “Significance of p16 and cyclin D1 expressions in human bladder transitional cell carcinoma,” Chinese Journal of Cancer Prevention and Treatment, vol. 10, pp. 1174–1176, 2003 (Chinese). View at Google Scholar
  32. H. M. Yang, “p16 and nm23 expression in bladder carcinoma,” Journal of Oncology Practice, vol. 19, pp. 344–345, 2005 (Chinese). View at Google Scholar
  33. X. H. Wang, Y. Cui, and X. J. Meng, “The expression and significance of PTEN, p16 and mutant p53 in bladder cancer,” Shandong Medical Journal, vol. 53, pp. 37–39, 2013 (Chinese). View at Google Scholar
  34. J. Y. Leng, Y. Z. Zhang, X. D. Yao, and K. S. Wen, “Expression of bcl-2 and p16 in transitional cell carcinoma of urinary bladder,” Chinese Journal of Surgery, vol. 38, no. 1, pp. 40–43, 2000 (Chinese). View at Google Scholar · View at Scopus
  35. Y. Bai and Y. J. Xiong, “Expression and significance of mfn2 and p16 in bladder cancer,” Shandong Medical Journal, vol. 54, pp. 61–62, 2014 (Chinese). View at Google Scholar
  36. C. Y. Wang, X. J. Liu, L. G. Wang et al., “p16, p53 and c-erbB-2 gene expression in bladder carcinoma,” Chinese Journal of Pathology, vol. 29, no. 1, pp. 20–23, 2000 (Chinese). View at Google Scholar · View at Scopus
  37. Y. C. Wang, H. K. Lu, and D. J. Gao, “Clinical significance of hTERT and p16, cyclinD1, Rb expression in the transitional cell carcinoma of urinary bladder,” Acta Academiae Medicinae Weifang, vol. 28, pp. 103–106, 2006 (Chinese). View at Google Scholar
  38. T. Lu, W. M. Yang, and Z. Q. Ye, “The expression of p16, p53 and PCNA proteins in transitional cell carcinoma of bladder and their significance,” Journal of Clinical Urology, vol. 23, pp. 58–60, 2008 (Chinese). View at Google Scholar
  39. Q. X. Xie, F. D. Lin, Z. X. Hang, and X. Z. Lin, “Correlation and expression of p16, pRb and cyclinD1 in bladder cancer,” China Journal of Modern Medicine, vol. 13, pp. 25–27, 2003 (Chinese). View at Google Scholar
  40. X. F. Qiu, E. S. Han, and F. B. Chen, “Expression and clinical significance of p16 protein in transitional cell carcinoma of the bladder,” Ningxia Medical Journal, vol. 28, pp. 578–579, 2006 (Chinese). View at Google Scholar
  41. S. Rebouissou, A. Hérault, E. Letouzé et al., “CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma,” Journal of Pathology, vol. 227, no. 3, pp. 315–324, 2012. View at Publisher · View at Google Scholar · View at Scopus
  42. D. Abat, O. Demirhan, N. Inandiklioglu et al., “Genetic alterations of chromosomes, p53 and p16 genes in low- and high-grade bladder cancer,” Oncology Letters, vol. 8, no. 1, pp. 25–32, 2014. View at Publisher · View at Google Scholar · View at Scopus
  43. F. K. Mostofi, L. H. Sobin, and H. Torloni, “Histological typing of urinary bladder tumours,” International Classification of Tumours 10, World Health Organization, Geneva, Switzerland, 1973. View at Google Scholar
  44. J. Eble, G. Sauter, J. Epstein et al., Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, IARC Press, Lyon, France, 2004.
  45. A. Kamb, N. A. Gruis, J. Weaver-Feldhaus et al., “A cell cycle regulator potentially involved in genesis of many tumor types,” Science, vol. 264, no. 5157, pp. 436–440, 1994. View at Publisher · View at Google Scholar · View at Scopus
  46. V. H. Nargund, C. K. Tanabalan, and M. N. Kabir, “Management of non-muscle-invasive (Superficial) bladder cancer,” Seminars in Oncology, vol. 39, no. 5, pp. 559–572, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. D. G. Johnson and J. DeGregori, “Putting the oncogenic and tumor suppressive activities of E2F into context,” Current Molecular Medicine, vol. 6, no. 7, pp. 731–738, 2006. View at Google Scholar · View at Scopus
  48. J. G. Pan, R. F. Han, and Y. Wang, “Significance of p16 gene and p21 gene expression abnormality in the prognosis of bladder carcinoma: a meta-analysis,” Chinese Journal of Urology, vol. 27, pp. 400–403, 2006 (Chinese). View at Google Scholar
  49. K. T. Flaherty, P. M. LoRusso, A. DeMichele et al., “Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer,” Clinical Cancer Research, vol. 18, no. 2, pp. 568–576, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. M. A. Dickson, W. D. Tap, M. L. Keohan et al., “Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma,” Journal of Clinical Oncology, vol. 31, no. 16, pp. 2024–2028, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. G. Eilers, J. T. Czaplinski, M. Mayeda et al., “CDKN2A/p16 loss implicates CDK4 as a therapeutic target in imatinib-resistant dermatofibrosarcoma protuberans,” Molecular Cancer Therapeutics, vol. 14, no. 6, pp. 1346–1353, 2015. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Zennami, K. Yoshikawa, E. Kondo et al., “A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system,” Oncology Reports, vol. 26, no. 2, pp. 327–333, 2011. View at Publisher · View at Google Scholar · View at Scopus