Skip Navigation



Annals of Oncology Advance Access published online on September 19, 2006
Annals of Oncology, doi:10.1093/annonc/mdl289
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/11/1677    most recent
mdl289v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Maluf, F. C.
Right arrow Articles by Bajorin, D. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maluf, F. C.
Right arrow Articles by Bajorin, D. F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 European Society for Medical Oncology
Received March 30, 2006
Revised July 3, 2006
Accepted July 4, 2006

original article

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

F. C. Maluf 1, C. Cordon-Cardo 2, D. A. Verbel 3, J. M. Satagopan 3, M. G. Boyle 4, H. Herr 4, and D. F. Bajorin 5 *

1 The Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, New York; Division of Urology, Hospital das Clínicas, University of São Paulo and Department of Medical Oncology, Hospital Sírio-Libanês, São Paulo-SP-Brazil
2 Department of Pathology, Memorial Sloan-Kettering Cancer Center New York and the Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, USA
3 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center New York and the Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, USA
4 Department of Urology, Memorial Sloan-Kettering Cancer Center New York and the Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, USA
5 The Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and the Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, New York

* To whom correspondence should be addressed.
D. F. Bajorin, E-mail: bajorind{at}mskcc.org


  Abstract

Background: Tumor proliferation and apoptosis may be influenced by the mdm-2 gene product, which can block the antiproliferative effects of p53. bcl-2, one of a family of related genes that regulates the apoptotic pathway, exhibits a negative influence. Both individual and cooperative effects of these gene products may affect the biological behavior of primary bladder cancers and long-term outcome to standard therapy.

Methods: This study retrospectively evaluated the association with survival of mdm-2, p53, and bcl-2 expression in 59 patients with muscle-invasive, node-negative transitional cell carcinoma (TCC) treated with neo-adjuvant chemotherapy followed by locoregional surgery. Each marker was defined as an altered phenotype if ≥20% malignant cells in the primary tumor exhibited staining; normal or minimal expression was defined as <20% cells exhibiting staining.

Results: Altered mdm-2, p53, and bcl-2 expression was observed in 37%, 54%, and 46% of patients, respectively. In single marker analysis, altered p53 expression correlated with long-term survival (P = 0.05) but mdm-2 (P = 0.42) or bcl-2 (P = 0.17) did not. In the multiple-marker analysis, a prognostic index simultaneously assessing mdm-2, p53, and bcl-2 correlated with survival (P = 0.01). The 5-year survival for patients in which all markers were normally expressed was 54% compared with 25% in those with all three markers aberrantly expressed. Patients with aberrant expression of either one or two markers had an intermediate 5-year survival (49%). There was no association of molecular markers either alone or in combination with pathologic downstaging after neo-adjuvant chemotherapy.

Conclusion: The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder.

Keywords: bcl-2; mdm-2; p53; prognosis; transitional cell carcinoma; urothelial tract cancer.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
A. Veerakumarasivam, H. E. Scott, S.-F. Chin, A. Warren, M. J. Wallard, D. Grimmer, K. Ichimura, C. Caldas, V. P. Collins, D. E. Neal, et al.
High-Resolution Array-Based Comparative Genomic Hybridization of Bladder Cancers Identifies Mouse Double Minute 4 (MDM4) as an Amplification Target Exclusive of MDM2 and TP53
Clin. Cancer Res., May 1, 2008; 14(9): 2527 - 2534.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.