Skip to main content

Advertisement

Log in

P27Kip1 and Ki-67 expression analysis in transitional cell carcinoma of the bladder

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

P27Kip1 protein is a cell cycle inhibitor which blocks the transition of cells from G1 to S phase, while Ki-67 is the most specific marker of proliferative activity. Both proteins are independent predictors of clinical outcome in various neoplasms. The aim of the study was to assess the prognostic value of p27Kip1 and Ki-67 expression in urothelial bladder tumours. P27Kip1 and Ki-67 expressions were evaluated immunohistochemically in archival samples of 45 superficial and 26 invasive transitional cell carcinomas obtained by a transurethral resection. In the patients with superficial tumours, disease-free survival (DFS) was positively influenced by good histological differentiation as well as by concurrent high p27Kip1 and low Ki-67 expression. Multivariate analysis has confirmed that tumour grade and p27Kip1/Ki-67 status were independent predictors of DFS (p=0.028 and p=0.029, respectively). P27Kip1 or Ki-67 expressions did not influence overall survival. We conclude that a variable combined of p27Kip1 and Ki-67 expressions is a better predictor of DFS in superficial bladder tumours than either protein alone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. Aaltomaa S, Lipponen P, Vesalainen S, Ala-Opas M, Eskelinen M, Syrjanen K (1997) Value of Ki-67 immunolabelling as a prognostic factor in prostate cancer. Eur Urol 32: 410

    CAS  PubMed  Google Scholar 

  2. Asakura T, Takano Y, Iki M, Suwa Y, Noguchi S, Kubota Y, Masuda M (1997) Prognostic value of Ki-67 for recurrence and progression of superficial bladder cancer. J Urol 158: 385

    CAS  PubMed  Google Scholar 

  3. Bassi P, Ferrante GD, Piazza N, Spinadin R, Carando R, Pappagallo G, Pagano F (1999) Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort. J Urol 161: 1494

    CAS  PubMed  Google Scholar 

  4. Bettencourt MC, Bauer JJ, Sesterhenn IA, Mostofi FK, McLeod DG, Moul JW (1996) Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy. J Urol 156: 1064

    CAS  PubMed  Google Scholar 

  5. Blanchet P, Droupy S, Eschewege P, Viellefond A, Paradis V, Pichon M-F, Jardin A, Benoit G (2001) Prospective evaluation of Ki-67 labeling in predicting the recurrence and progression of superficial bladder transitional cell carcinoma. Eur Urol 40: 169

    Article  CAS  PubMed  Google Scholar 

  6. Cox D (1972) Regression models and life tables (with discussion). J Royal Statist Soc 34: 187

    Google Scholar 

  7. Del Pizzo JJ, Borkowski A, Jacobs SC, Kyprianou N (1999) Loss of cell cycle regulators p27(Kip1) and cyclin E in transitional cell carcinoma of the bladder correlates with tumor grade and patient survival. Am J Pathol 155: 1129

    Google Scholar 

  8. Endl E, Kausch I, Baack M, Knippers R, Gerdes J, Scholzen T (2001) The expression of Ki-67, MCM3, and p27 defines distinct subsets of proliferating, resting, and differentiated cells. J Pathol 195: 457

    Article  CAS  PubMed  Google Scholar 

  9. Esposito V, Baldi A, De Luca A, Groger AM, Loda M, Giordano GG, Caputi M, Baldi F, Pagano M, Giordano A (1997) Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res 57: 3381

    CAS  PubMed  Google Scholar 

  10. Franke KH, Miklosi M, Goebell P, Clasen S, Steinhoff C, Anastasiadis AG, Gerharz C, Schulz WA (2000) Cyclin-dependent kinase inhibitor P27(KIP1) is expressed preferentially in early stages of urothelial carcinoma. Urology 56: 689

    Article  CAS  PubMed  Google Scholar 

  11. Gontero P, Casetta G, Zitella A, Ballario R, Pacchioni D, Magnani C, Muir GH, Tizzani A (2000) Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic index as markers of tumour recurrence in superficial transitional cell carcinoma of the bladder. Eur Urol 38: 287

    Article  CAS  PubMed  Google Scholar 

  12. Heney NM, Ahmed S, Flanagan MJ, Frable W, Corder MP, Hafermann MD, Hawkins IR (1983) Superficial bladder cancer: progression and recurrence. J Urol 130: 1083

    CAS  PubMed  Google Scholar 

  13. Jansen RL, Hupperets PS, Arends JW, Joosten-Achjanie SR, Volovics A, Schouten HC, Hillen HF (1998) MIB-1 labelling index is an independent prognostic marker in primary breast cancer. Br J Cancer 78: 460

    CAS  PubMed  Google Scholar 

  14. Kamai T, Takagi K, Asami H, Ito Y, Oshima H, Yoshida KI (2001) Decreasing of p27(Kip1)and cyclin E protein levels is associated with progression from superficial into invasive bladder cancer. Br J Cancer 84: 1242

    CAS  PubMed  Google Scholar 

  15. Kiemeney LA, Witjes JA, Heijbroek RP, Verbeek AL, Debruyne FM (1993) Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer. J Urol 150: 60

    CAS  PubMed  Google Scholar 

  16. Korkolopoulou P, Christodoulou P, Konstantinidou AE, Thomas-Tsagli E, Kapralos P, Davaris P (2000) Cell cycle regulators in bladder cancer: a multivariate survival study with emphasis on p27Kip1. Hum Pathol 31: 751

    CAS  PubMed  Google Scholar 

  17. Kurth KH, Denis L, Bouffioux C, Sylvester R, Debruyne FM, Pavone-Macaluso M, Oosterlinck W (1995) Factors affecting recurrence and progression in superficial bladder tumours. Eur J Cancer 31A: 1840

    Article  CAS  PubMed  Google Scholar 

  18. Liukkonen T, Rajala P, Raitanen M, Rintala E, Kaasinen E, Lipponen P, for the Finnbladder Group (1999) Prognostic value of MIB-1 score, p53, EGFr, mitotic index and papillary status in primary superficial (stage pTa/T1) bladder cancer: a prospective comparative study. Eur Urol 36: 393

    CAS  PubMed  Google Scholar 

  19. Lloyd RV, Erickson LA, Jin L, Kulig E, Qian X, Cheville JC, Scheithauer BW (1999) p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol 154: 313

    CAS  PubMed  Google Scholar 

  20. Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M (1997) Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med 3: 231

    CAS  PubMed  Google Scholar 

  21. Mantel N, Haenszel W (1959) Statistical aspect of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719

    CAS  Google Scholar 

  22. Mostofi FK, Davis CJ, Sesterhenn A, (1999) Histological typing of urinary bladder tumors, 2nd edn. Springer, Berlin Heidelberg New York, p 104

  23. Oosterhuis JWA, Schapers RFM, Janssen-Heijnen MLG, Smeets AWGB, Pauwels RPE (2000) MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder: clinical significance and comparison with other prognostic factors. Cancer 88: 2598

    Article  CAS  PubMed  Google Scholar 

  24. Pfister C, Lacombe L, Vezina M-C, Moore L, Larue H, Tetu B, Meyer F, Fradet Y (1999) Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors. Hum Pathol 30: 1350

    CAS  PubMed  Google Scholar 

  25. Ponce-Castaneda MV, Lee MH, Latres E, Polyak K, Lacombe L, Montgomery K, Mathew S, Krauter K, Sheinfeld J, Massague J et al (1995) p27Kip1: chromosomal mapping to 12p12–12p13.1 and absence of mutations in human tumors. Cancer Res 55: 1211

    CAS  PubMed  Google Scholar 

  26. Popov Z, Hoznek A, Colombel M, Bastuji-Garin S, Lefrere-Belda MA, Bellot J, Abboh CC, Mazerolles C, Chopin DK (1997) The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder. Cancer 80: 1472

    Article  CAS  PubMed  Google Scholar 

  27. Santos L, Amaro T, Costa C, Pareira S, Bento MJ, Lopes P, Oliveira J, Criado B, Lopes C (2003) Ki-67 index enhances the prognostic accuracy of the urothelial superficial bladder carcinoma risk group classification. Int J Cancer 105: 267

    Article  CAS  PubMed  Google Scholar 

  28. Schmitz-Drager BJ, Goebell PJ, Ebert T, Fradet Y (2000) p53 immunohistochemistry as a prognostic marker in bladder cancer. Playground for urology scientists? Eur Urol 38: 691

    PubMed  Google Scholar 

  29. Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182: 311

    CAS  PubMed  Google Scholar 

  30. Seshadri R, Leong AS, McCaul K, Firgaira FA, Setlur V, Horsfall DJ (1996) Relationship between p53 gene abnormalities and other tumour characteristics in breast-cancer prognosis. Int J Cancer 69: 135

    Article  CAS  PubMed  Google Scholar 

  31. Sgambato A, Migaldi M, Faraglia B, Garagnani L, Romano G, De Gaetani C, Ferrari P, Capelli G, Trentini GP, Cittadini A (1999) Loss of P27Kip1 expression correlates with tumor grade and with reduced disease-free survival in primary superficial bladder cancers. Cancer Res 59: 3245

    CAS  PubMed  Google Scholar 

  32. Sgambato A, Migaldi M, Faraglia B, De Aloysio G, Ferrari P, Ardito R, De Gaetani C, Capelli G, Cittadini A, Trentini GP (2002) Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. Int J Cancer 97: 671

    Article  CAS  PubMed  Google Scholar 

  33. Sobin LH, Wittekind C (1997) TNM Classification of malignant tumors, 5th edn. John Wiley & Sons, New York

  34. Suwa Y, Takano Y, Iki M, Asakura T, Noguchi S, Masuda M (1997) Prognostic significance of Ki-67 expression in transitional cell bladder carcinoma after radical cystectomy. Pathol Res Pract 193: 551

    CAS  PubMed  Google Scholar 

  35. Tan P, Cady B, Wanner M, Worland P, Cukor B, Magi-Galluzzi C, Lavin P, Draetta G, Pagano M, Loda M (1997) The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res 57: 1259

    CAS  PubMed  Google Scholar 

  36. Ueda T, Aozasa K, Tsujimoto M, Ohsawa M, Uchida A, Aoki Y, Ono K, Matsumoto K (1989) Prognostic significance of Ki-67 reactivity in soft tissue sarcomas. Cancer 63: 1607

    CAS  PubMed  Google Scholar 

  37. Vieweg J, Gschwend JE, Herr HW, Fair WR (1999) The impact of primary stage on survival in patients with lymph node positive bladder cancer. J Urol 161: 72

    CAS  PubMed  Google Scholar 

  38. Wu TT, Chen JH, Lee YH, Huang JK (2000) The role of bcl-2, p53, and ki-67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma. J Urol 163: 758

    CAS  PubMed  Google Scholar 

  39. Yang RM, Naitoh J, Murphy M, Wang HJ, Phillipson J, de Kernion JB, Loda M, Reiter RE (1998) Low p27 expression predicts poor disease-free survival in patients with prostate cancer. J Urol 159: 941

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bartosz Dybowski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dybowski, B., Kupryjańczyk, J., Rembiszewska, A. et al. P27Kip1 and Ki-67 expression analysis in transitional cell carcinoma of the bladder. Urol Res 31, 397–401 (2003). https://doi.org/10.1007/s00240-003-0356-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00240-003-0356-8

Keywords

Navigation