Originally published as JCO Early Release 10.1200/JCO.2004.03.118 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 Shariat, S. F. Articles by Lerner, S. P. Search for Related Content PubMed PubMed Citation Articles by Shariat, S. F. Articles by Lerner, S. P. Related Articles Related Article Related Editorial Social Bookmarking                            What's this?

p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer

From the Scott Department of Urology and Department of Pathology, Baylor College of Medicine; the Methodist Hospital; and the Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston; and the Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.

Address reprint requests to Seth P. Lerner, MD, Scott Department of Urology, Baylor College of Medicine, 6560 Fannin, Suite 2100, Houston, TX 77030; e-mail: slerner{at}bcm.tmc.edu

PURPOSE: To determine whether p53, p21, pRB, and/or p16 expression is associated with bladder cancer stage, progression, and prognosis.

PATIENTS AND METHODS: Immunohistochemical staining for p53, p21, pRB, and p16 was carried out on serial sections from archival specimens of 80 patients who underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer (median follow-up, 101 months).

RESULTS: p53, p21, and pRB or p16 expression was altered in 45 (56%), 39 (49%), and 43 (54%) tumors, respectively. Sixty-six patients (83%) had at least one marker altered, and 21 patients (26%) had all three altered. Abnormal expressions of p53, p21, and pRB/p16 expression were associated with muscle-invasive disease (P = .007, P = .003, and P = .003, respectively). The alteration of each marker was independently associated with disease progression (P .038) and disease-specific survival (P .039). In multivariable models that included standard pathologic features and p53 with p21 or p53 with pRB/p16, only p53 and lymph node metastases were associated with bladder cancer progression (P .026) and death (P .028). In models that included p21 and pRB/p16, only p21 and lymph node metastases were associated with bladder cancer progression (P .022) and death (P .028). In a model that included the combined variables p53/p21 and pRB/p16, only p53/p21 and lymph node status were associated with bladder cancer progression (P .047) and death (P .036). The incremental number of altered markers was independently associated with an increased risk of bladder cancer progression (P = .005) and mortality (P = .007).

CONCLUSION: Although altered expression of each of the four cell cycle regulators is associated with bladder cancer outcome in patients undergoing radical cystectomy, p53 is the strongest predictor, followed by p21, suggesting a more pivotal role of the p53/p21 pathway in bladder cancer progression.

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

Related Article

• Combined Effects of p53, p21, and pRb Expression in the Progression of Bladder Transitional Cell Carcinoma
  Sunanda J. Chatterjee, Ram Datar, David Youssefzadeh, Ben George, Peter J. Goebell, John P. Stein, Lillian Young, Shan-Rong Shi, Conway Gee, Susan Groshen, Donald G. Skinner, and Richard J. Cote
  JCO 2004 22: 1007-1013 [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]

				K. Nakazawa, S.-i. Murata, T. Yuminamochi, Y. Ishii, S. Ohno, T. Nakazawa, T. Kondo, and R. Katoh p16INK4a Expression Analysis as an Ancillary Tool for Cytologic Diagnosis of Urothelial Carcinoma Am J Clin Pathol, November 1, 2009; 132(5): 776 - 784. [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]

				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]

				C Mian, M Lodde, E Comploj, L Lusuardi, S Palermo, M Mian, K Maier, and A Pycha Multiprobe fluorescence in situ hybridisation: prognostic perspectives in superficial bladder cancer. J. Clin. Pathol., September 1, 2006; 59(9): 984 - 987. [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]

				A.-F. Dekairelle, B. Tombal, J.-P. Cosyns, and J.-L. Gala Assessment of the Transcriptional Activity of p53 Improves the Prediction of Recurrence in Superficial Transitional Cell Carcinoma of the Bladder Clin. Cancer Res., July 1, 2005; 11(13): 4724 - 4732. [Abstract] [Full Text] [PDF]

				G. Ohlsson, J. M. A. Moreira, P. Gromov, G. Sauter, and J. E. Celis Loss of Expression of the Adipocyte-type Fatty Acid-binding Protein (A-FABP) Is Associated with Progression of Human Urothelial Carcinomas Mol. Cell. Proteomics, April 1, 2005; 4(4): 570 - 581. [Abstract] [Full Text] [PDF]

				M Gallucci, F Guadagni, R Marzano, C Leonardo, R Merola, S Sentinelli, E M Ruggeri, R Cantiani, I Sperduti, F d. l. I Lopez, et al. Status of the p53, p16, RB1, and HER-2 genes and chromosomes 3, 7, 9, and 17 in advanced bladder cancer: correlation with adjacent mucosa and pathological parameters J. Clin. Pathol., April 1, 2005; 58(4): 367 - 371. [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]