Originally published as JCO Early Release 10.1200/JCO.2004.05.174 on February 23 2004

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chatterjee, S. J. Articles by Cote, R. J. Search for Related Content PubMed PubMed Citation Articles by Chatterjee, S. J. Articles by Cote, R. J. Related Articles Related Article Related Editorial Social Bookmarking                            What's this?

Combined Effects of p53, p21, and pRb Expression in the Progression of Bladder Transitional Cell Carcinoma

From the Departments of Pathology, Urology, and Preventive Medicine, University of Southern California Keck School of Medicine; and University of Southern California/Kenneth Norris Comprehensive Cancer Center, Los Angeles, CA

Address reprint requests to Richard J. Cote, MD, FRCPath, Department of Pathology, University of Southern California/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Ave, Los Angeles, CA 90033; e-mail: cote_r{at}norsur.hsc.usc.edu

PURPOSE: To determine the combined effects of p53, p21, and pRb alterations in predicting the progression of bladder transitional cell carcinoma.

PATIENTS AND METHODS: p53, p21, and pRb expression was examined immunohistochemically on archival radical cystectomy samples from 164 patients with invasive or high-grade recurrent superficial transitional cell carcinoma (TCC; lymph node–negative, 117 patients; lymph node–positive, 47 patients). Median follow-up was 8.6 years. Based on percentage of nuclear reactivity, p53 was considered as wild-type (0% to 10%) or altered (> 10%); p21 was scored as wild-type (>10%) or altered (< 10%); and pRb status was considered wild-type (1% to 50%) or altered (0% or > 50%).

RESULTS: As individual determinants, the p53, p21, and pRb status were independent predictors of time to recurrence (P < .001, P < .001, and P < .001, respectively), and overall survival (P < .001, P = .002, and P = .001, respectively). By examining these determinants in combination, patients were categorized as group I (no alteration in any determinant, 47 patients), group II (any one determinant altered, 51 patients), group III (any two determinants altered, 42 patients), and group IV (all three determinants altered, 24 patients). The 5-year recurrence rates in these groups were 23%, 32%, 57%, and 93%, respectively (log-rank P < .001), and the 5-year survival rates were 70%, 58%, 33%, and 8%, respectively (log-rank P < .001). After stratifying by stage, the number of altered proteins remained significantly associated with time to recurrence and overall survival.

CONCLUSION: This study suggests that alterations in p53, p21, and pRb act in cooperative or synergistic ways to promote bladder cancer progression. Examining these determinants in combination provides additional information above the use of a single determinant alone.

Supported by the Molecular and Cellular Pathways of Bladder Cancer Progression Grant (grant No. NCI CA 70903), the Cancer Center Core Grant (grant No. NCI CA 14089), and the Bladder Cancer Program Project Grant (grant No. PO1 CA 86871).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

• p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer
  Shahrokh F. Shariat, Hideo Tokunaga, JainHua Zhou, JaHong Kim, Gustavo E. Ayala, William F. Benedict, and Seth P. Lerner
  JCO 2004 22: 1014-1024 [Abstract] [Full Text]

Related Editorial

• p53 and RB: Simple Interesting Correlates or Tumor Markers of Critical Predictive Nature?
  Carlos Cordon-Cardo
  JCO 2004 22: 975-977 [Full Text]

This article has been cited by other articles:

				S. F. Shariat, P. I. Karakiewicz, G. Godoy, J. A. Karam, R. Ashfaq, Y. Fradet, H. Isbarn, F. Montorsi, C. Jeldres, P. J. Bastian, et al. Survivin as a Prognostic Marker for Urothelial Carcinoma of the Bladder: A Multicenter External Validation Study Clin. Cancer Res., November 15, 2009; 15(22): 7012 - 7019. [Abstract] [Full Text] [PDF]

				L. CORMIO, I. TOLVE, P. ANNESE, A. SARACINO, R. ZAMPARESE, F. SANGUEDOLCE, P. BUFO, M. BATTAGLIA, F. P. SELVAGGI, and G. CARRIERI Altered p53 and pRb Expression Is Predictive of Response to BCG Treatment in T1G3 Bladder Cancer Anticancer Res, October 1, 2009; 29(10): 4201 - 4204. [Abstract] [Full Text] [PDF]

				A. P. Mitra, V. Pagliarulo, D. Yang, F. M. Waldman, R. H. Datar, D. G. Skinner, S. Groshen, and R. J. Cote Generation of a Concise Gene Panel for Outcome Prediction in Urinary Bladder Cancer J. Clin. Oncol., August 20, 2009; 27(24): 3929 - 3937. [Abstract] [Full Text] [PDF]

				J. E. Rosenberg and W. C. Hahn Bladder cancer: modeling and translation Genes & Dev., March 15, 2009; 23(6): 655 - 659. [Abstract] [Full Text] [PDF]

				Y. Tang, A. R. Simoneau, J. Xie, B. Shahandeh, and X. Zi Effects of the Kava Chalcone Flavokawain A Differ in Bladder Cancer Cells with Wild-type versus Mutant p53 Cancer Prevention Research, November 1, 2008; 1(6): 439 - 451. [Abstract] [Full Text] [PDF]

				A. P. Mitra, R. H. Datar, and R. J. Cote Molecular Pathways in Invasive Bladder Cancer: New Insights Into Mechanisms, Progression, and Target Identification J. Clin. Oncol., December 10, 2006; 24(35): 5552 - 5564. [Abstract] [Full Text] [PDF]

				F. Maluf, C Cordon-Cardo, D. Verbel, J. Satagopan, M. Boyle, H Herr, and D. Bajorin Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment Ann. Onc., November 1, 2006; 17(11): 1677 - 1686. [Abstract] [Full Text] [PDF]

				M. A. Knowles Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis, March 1, 2006; 27(3): 361 - 373. [Abstract] [Full Text] [PDF]

				N. Ramesh, Y. Ge, D. L. Ennist, M. Zhu, M. Mina, S. Ganesh, P. S. Reddy, and D.-C. Yu CG0070, a Conditionally Replicating Granulocyte Macrophage Colony-Stimulating Factor-Armed Oncolytic Adenovirus for the Treatment of Bladder Cancer Clin. Cancer Res., January 1, 2006; 12(1): 305 - 313. [Abstract] [Full Text] [PDF]

				U. H. Frey, A. Eisenhardt, G. Lummen, H. Rubben, K.-H. Jockel, K. W. Schmid, and W. Siffert The T393C Polymorphism of the G{alpha}s Gene (GNAS1) Is a Novel Prognostic Marker in Bladder Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 871 - 877. [Abstract] [Full Text] [PDF]

				D. Liu, S. J. O'Day, D. Yang, P. Boasberg, R. Milford, T. Kristedja, S. Groshen, and J. Weber Impact of Gene Polymorphisms on Clinical Outcome for Stage IV Melanoma Patients Treated with Biochemotherapy: An Exploratory Study Clin. Cancer Res., February 1, 2005; 11(3): 1237 - 1246. [Abstract] [Full Text] [PDF]

				C. Cordon-Cardo p53 and RB: Simple Interesting Correlates or Tumor Markers of Critical Predictive Nature? J. Clin. Oncol., March 15, 2004; 22(6): 975 - 977. [Full Text] [PDF]