Skip to main content
Top
Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer

Authors: Lujia Wang, Chenchen Feng, Guanxiong Ding, Qiang Ding, Zhongwen Zhou, Haowen Jiang, Zhong Wu

Published in: Tumor Biology | Issue 4/2014

Login to get access

Abstract

Tumor markers Ki67, TP53, and TP63 are common labels in the diagnosis of bladder cancer (BCa) around the world. The combination of those biomarkers may have advantages in predicting BCa prognosis and non-muscle-invasive bladder cancer (NMIBC) postoperative recurrence. We investigated the immunohistochemical profiles of 313 bladder cancer samples classified under the WHO/ISUP (2004) grading scale and the UICC-TNM (2002) classification. Then we investigated their predictive value in the tumor recurrence of 270 NMIBC patients after TURBT. Expression of Ki67 correlates with grade, stage, tumor size, and tumor numbers. Semiquantitative evaluation of TP53 correlates with grade and invasive conditions. The positive expression rate of TP63 correlated with tumor grade and stage. The combined effect of TP53 and Ki67 revealed a predictive value in NMIBC recurrence. However, the positive TP63 expression did not show any protective effect in NMIBC recurrence. The expression of TP53 and Ki67 could be used to predict the risk of NMIBC recurrence postoperatively.
Literature
1.
go back to reference Cordon-Cardo C et al. Molecular alterations associated with bladder cancer initiation and progression. Scand J Urol Nephrol Suppl. 2008;8:154–65.CrossRef Cordon-Cardo C et al. Molecular alterations associated with bladder cancer initiation and progression. Scand J Urol Nephrol Suppl. 2008;8:154–65.CrossRef
2.
go back to reference Epstein JI, Amin VR, Reuter FK, et al. The World Health Organization/International Society of Urological Pathology Consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. The Bladder Consensus Conference Committee. Am J Surg Pathol. 1998;22:1435–48.PubMedCrossRef Epstein JI, Amin VR, Reuter FK, et al. The World Health Organization/International Society of Urological Pathology Consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. The Bladder Consensus Conference Committee. Am J Surg Pathol. 1998;22:1435–48.PubMedCrossRef
3.
go back to reference Larsson P, Wijkstrom H, Thorstenson A, et al. A population-based study of 538 patients with newly detected urinary bladder neoplasms followed during 5 years. Scand J Urol Nephrol. 2003;37:195–201.PubMedCrossRef Larsson P, Wijkstrom H, Thorstenson A, et al. A population-based study of 538 patients with newly detected urinary bladder neoplasms followed during 5 years. Scand J Urol Nephrol. 2003;37:195–201.PubMedCrossRef
4.
go back to reference Fernandez-Gomez J, Madero R, Solsona E, et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J Urol. 2009;182(5):2195–203.PubMedCrossRef Fernandez-Gomez J, Madero R, Solsona E, et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J Urol. 2009;182(5):2195–203.PubMedCrossRef
5.
go back to reference Madersbacher S, Hochreiter W, Burkhard F, et al. Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol. 2003;21(4):690–6.PubMedCrossRef Madersbacher S, Hochreiter W, Burkhard F, et al. Radical cystectomy for bladder cancer today—a homogeneous series without neoadjuvant therapy. J Clin Oncol. 2003;21(4):690–6.PubMedCrossRef
6.
go back to reference Bassi P, Ferrante GD, Piazza N, et al. Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort. J Urol. 1999;161(5):1494–7.PubMedCrossRef Bassi P, Ferrante GD, Piazza N, et al. Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort. J Urol. 1999;161(5):1494–7.PubMedCrossRef
7.
go back to reference Evans CP, Debruyne F, Payne H, et al. Bladder cancer: management and future directions. Eur Urol Suppl. 2007;6:365–73.CrossRef Evans CP, Debruyne F, Payne H, et al. Bladder cancer: management and future directions. Eur Urol Suppl. 2007;6:365–73.CrossRef
8.
go back to reference Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, et al. Multivariate analysis of the prognostic factors of primary superficial bladder cancer. J Urol. 2000;163:73–8.PubMedCrossRef Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, et al. Multivariate analysis of the prognostic factors of primary superficial bladder cancer. J Urol. 2000;163:73–8.PubMedCrossRef
9.
go back to reference Pruthi RS, Baldwin N, Bhalani V, et al. Conservative management of low risk superficial bladder tumors. J Urol. 2008;179(1):87–90.PubMedCrossRef Pruthi RS, Baldwin N, Bhalani V, et al. Conservative management of low risk superficial bladder tumors. J Urol. 2008;179(1):87–90.PubMedCrossRef
10.
go back to reference Sylvester R, Oosterlinck W, van der Meijden A, et al. Treatment of superficial bladder tumors: achievements and needs. The EORTC Genitourinary Group. Eur Urol. 2000;37 Suppl 3:1–9.PubMed Sylvester R, Oosterlinck W, van der Meijden A, et al. Treatment of superficial bladder tumors: achievements and needs. The EORTC Genitourinary Group. Eur Urol. 2000;37 Suppl 3:1–9.PubMed
11.
go back to reference Evans C, Debruyne F, Payne H, et al. Bladder cancer: management and future directions. Eur Urol Suppl. 2006;6:365–73.CrossRef Evans C, Debruyne F, Payne H, et al. Bladder cancer: management and future directions. Eur Urol Suppl. 2006;6:365–73.CrossRef
12.
13.
go back to reference Sauter G, Algaba F, Amin M., et al. Tumours of the urinary system: non-invasive urothelial neoplasias. In: Eble JN, Sauter G, Epstein Jl, Sesterhenn I, eds. WHO classification of classification of tumours of the urinary system and male genital organs. Lyon: IARCC Press, 2004, pp. 29–34. Sauter G, Algaba F, Amin M., et al. Tumours of the urinary system: non-invasive urothelial neoplasias. In: Eble JN, Sauter G, Epstein Jl, Sesterhenn I, eds. WHO classification of classification of tumours of the urinary system and male genital organs. Lyon: IARCC Press, 2004, pp. 29–34.
14.
go back to reference Sobin LH, Gospodariwicz M, Wittekind C. (eds). TNM classification of malignant tumors. UICC International Union Against Cancer. 7th edn. Wiley-Blackwell, 2009; pp. 262–265. Sobin LH, Gospodariwicz M, Wittekind C. (eds). TNM classification of malignant tumors. UICC International Union Against Cancer. 7th edn. Wiley-Blackwell, 2009; pp. 262–265.
15.
go back to reference Wang L, Feng C, Ding G, et al. Relationship of TP53 and Ki67 expression in bladder cancer under WHO 2004 classification. J BUON. 2013;18(2):420–4.PubMed Wang L, Feng C, Ding G, et al. Relationship of TP53 and Ki67 expression in bladder cancer under WHO 2004 classification. J BUON. 2013;18(2):420–4.PubMed
16.
go back to reference Feng CC, Wang PH, Ding Q, Guan M, Zhang YF, Jiang HW, et al. Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis. Urol Oncol. 2013;31(2):241–6.PubMedCrossRef Feng CC, Wang PH, Ding Q, Guan M, Zhang YF, Jiang HW, et al. Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis. Urol Oncol. 2013;31(2):241–6.PubMedCrossRef
17.
go back to reference Feng C, Wu Z, Guo T, Jiang H, Guan M, Zhang Y, et al. BLCA-4 expression is related to MMP-9, VEGF, IL-1α and IL-8 in bladder cancer but not to PEDF. TNF-α or angiogenesis. Pathol Biol (Paris). 2012;60:e36–40.CrossRef Feng C, Wu Z, Guo T, Jiang H, Guan M, Zhang Y, et al. BLCA-4 expression is related to MMP-9, VEGF, IL-1α and IL-8 in bladder cancer but not to PEDF. TNF-α or angiogenesis. Pathol Biol (Paris). 2012;60:e36–40.CrossRef
18.
go back to reference Feng CC, Wang PH, Guan M, Jiang HW, Wen H, Ding Q, et al. Urinary BLCA-4 is highly specific for detection of bladder cancer in Chinese Han population and is related to tumour invasiveness. Folia Biol (Praha). 2011;57:242–7. Feng CC, Wang PH, Guan M, Jiang HW, Wen H, Ding Q, et al. Urinary BLCA-4 is highly specific for detection of bladder cancer in Chinese Han population and is related to tumour invasiveness. Folia Biol (Praha). 2011;57:242–7.
19.
go back to reference Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage TaT1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466–5.PubMedCrossRef Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage TaT1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466–5.PubMedCrossRef
20.
go back to reference Montironi R, Mazzucchelli R, Colanzi P, et al. Improving interobserver agreement and certainly level in diagnosing and grading papillary urothelial neoplasms. Usefulness of a Bayesian belief network. Eur Urol. 2002;41:449–57.PubMedCrossRef Montironi R, Mazzucchelli R, Colanzi P, et al. Improving interobserver agreement and certainly level in diagnosing and grading papillary urothelial neoplasms. Usefulness of a Bayesian belief network. Eur Urol. 2002;41:449–57.PubMedCrossRef
21.
go back to reference Yurakh A, Ramos D, Calabuig-Frinas S, et al. Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder. Eur Urol. 2006;50:506–15.PubMedCrossRef Yurakh A, Ramos D, Calabuig-Frinas S, et al. Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder. Eur Urol. 2006;50:506–15.PubMedCrossRef
22.
go back to reference Oosterhuis J, Schapers R, Janssen-Heijnen M, et al. MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder. Clinical significance and comparison with other prognostic factors. Cancer. 2000;88:2598–605.PubMedCrossRef Oosterhuis J, Schapers R, Janssen-Heijnen M, et al. MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder. Clinical significance and comparison with other prognostic factors. Cancer. 2000;88:2598–605.PubMedCrossRef
23.
go back to reference Wu T, Chen J, Lee Y, et al. The role of BCL-2, TP53 and Ki67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma. J Urol. 2000;163:758–60.PubMedCrossRef Wu T, Chen J, Lee Y, et al. The role of BCL-2, TP53 and Ki67 index in predicting tumor recurrence for low grade superficial transitional cell bladder carcinoma. J Urol. 2000;163:758–60.PubMedCrossRef
24.
go back to reference Gonzalez-Campora R, Davalos-Casanova A, et al. Apoptotic and proliferation indexes in primary superficial bladder tumors. Cancer Lett. 2006;242:266–72.PubMedCrossRef Gonzalez-Campora R, Davalos-Casanova A, et al. Apoptotic and proliferation indexes in primary superficial bladder tumors. Cancer Lett. 2006;242:266–72.PubMedCrossRef
25.
go back to reference Santos L, Amaro T, Pereira S, et al. Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder. EJSO. 2003;29:74–80.PubMedCrossRef Santos L, Amaro T, Pereira S, et al. Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder. EJSO. 2003;29:74–80.PubMedCrossRef
26.
go back to reference Mulder A, Van Hootegem J, Sylvester R, et al. Prognostic factors in bladder carcinoma: histological parameters and expression of a cell cycle related nuclear antigen (Ki67). J Pathol. 1992;166:37–43.PubMedCrossRef Mulder A, Van Hootegem J, Sylvester R, et al. Prognostic factors in bladder carcinoma: histological parameters and expression of a cell cycle related nuclear antigen (Ki67). J Pathol. 1992;166:37–43.PubMedCrossRef
27.
go back to reference Vet JA, Bringuier PJ, Poddighe HF, et al. TP53 mutations have no additional prognostic value over stage in bladder cancer. Br J Cancer. 1994;70:496–500.PubMedCentralPubMedCrossRef Vet JA, Bringuier PJ, Poddighe HF, et al. TP53 mutations have no additional prognostic value over stage in bladder cancer. Br J Cancer. 1994;70:496–500.PubMedCentralPubMedCrossRef
28.
go back to reference Erill N, Colomer A, Verdú M, et al. Genetic and immunophenotype analyses of TP53 in bladder cancer: TP53 alterations are associated with tumor progression. Diagn Mol Pathol. 2004;13(4):217–23.PubMedCrossRef Erill N, Colomer A, Verdú M, et al. Genetic and immunophenotype analyses of TP53 in bladder cancer: TP53 alterations are associated with tumor progression. Diagn Mol Pathol. 2004;13(4):217–23.PubMedCrossRef
29.
go back to reference Comperat E, Camparo P, Haus R, et al. Immunohistochemical expression of p63, p53 and MIB-1in urinary bladder carcinoma. A tissue microarray study of 158 cases. Virchows Arch. 2006;448:319–24.PubMedCrossRef Comperat E, Camparo P, Haus R, et al. Immunohistochemical expression of p63, p53 and MIB-1in urinary bladder carcinoma. A tissue microarray study of 158 cases. Virchows Arch. 2006;448:319–24.PubMedCrossRef
30.
go back to reference Liukkonen T, Rajala P, Raitanen M, et al. Prognostic value of MIB-1 score, TP53, EGFr, mitotic index and papillary status in primary superficial (stage pTa/pT1) bladder cancer: a prospective comparative study. Eur Urol. 1999;36:393–400.PubMedCrossRef Liukkonen T, Rajala P, Raitanen M, et al. Prognostic value of MIB-1 score, TP53, EGFr, mitotic index and papillary status in primary superficial (stage pTa/pT1) bladder cancer: a prospective comparative study. Eur Urol. 1999;36:393–400.PubMedCrossRef
31.
go back to reference Shariat S, Kim J, Raptidis G, et al. Association of p63 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology. 2003;61:1140–5.PubMedCrossRef Shariat S, Kim J, Raptidis G, et al. Association of p63 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology. 2003;61:1140–5.PubMedCrossRef
32.
go back to reference Friedrich M, Riethdorf S, Erbersdobler A, et al. Relevance of p53 gene alterations for tumor recurrence in patients with superficial transitional cell carcinoma of the bladder. J Urol. 1996;155:1754–7.CrossRef Friedrich M, Riethdorf S, Erbersdobler A, et al. Relevance of p53 gene alterations for tumor recurrence in patients with superficial transitional cell carcinoma of the bladder. J Urol. 1996;155:1754–7.CrossRef
33.
go back to reference Gontero P, Casetta G, Zitella A, et al. Evaluation of TP53 protein over expression, Ki67 proliferative activity and mitotic index as markers of tumor recurrence in superficial transitional cell carcinoma of the bladder. Eur Urol. 2000;38:287–96.PubMedCrossRef Gontero P, Casetta G, Zitella A, et al. Evaluation of TP53 protein over expression, Ki67 proliferative activity and mitotic index as markers of tumor recurrence in superficial transitional cell carcinoma of the bladder. Eur Urol. 2000;38:287–96.PubMedCrossRef
34.
go back to reference Yang A, McKeon F, et al. P63 and P73: p53 mimics, menaces and more. Nat Rev Mol Cell Biol. 2000;1:100–207.CrossRef Yang A, McKeon F, et al. P63 and P73: p53 mimics, menaces and more. Nat Rev Mol Cell Biol. 2000;1:100–207.CrossRef
35.
go back to reference Park B, Lee S, Kim J, et al. Frequent alteration of p63 expression in human primary carcinomas. Cancer Res. 2000;60:3370–4.PubMed Park B, Lee S, Kim J, et al. Frequent alteration of p63 expression in human primary carcinomas. Cancer Res. 2000;60:3370–4.PubMed
36.
go back to reference Urist M, Di Como C, Lu M, et al. Loss of p63 expression is associated with tumor progression in bladder. Am J Patho. 2002;161:1199–206.CrossRef Urist M, Di Como C, Lu M, et al. Loss of p63 expression is associated with tumor progression in bladder. Am J Patho. 2002;161:1199–206.CrossRef
Metadata
Title
Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer
Authors
Lujia Wang
Chenchen Feng
Guanxiong Ding
Qiang Ding
Zhongwen Zhou
Haowen Jiang
Zhong Wu
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1384-9

Other articles of this Issue 4/2014

Tumor Biology 4/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine