Annals of Oncology Advance Access originally published online on September 19, 2006
Annals of Oncology 2006 17(11):1677-1686; doi:10.1093/annonc/mdl289
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© 2006 European Society for Medical Oncology
urogenital tumors |
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
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
2 Division of Urology, Hospital das Clínicas, University of São Paulo and Department of Medical Oncology, Hospital Sírio-Libanês, São Paulo–SP–Brazil
3 Department of Pathology, Joan and Sanford Weill Medical College of Cornell University, New York, USA
4 Department of Epidemiology and Biostatistics, Joan and Sanford Weill Medical College of Cornell University, New York, USA
5 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
* Correspondence to: Dr D. F. Bajorin, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Tel: (646) 422-4333; Fax: (212) 988-1079; E-mail: bajorind{at}mskcc.org
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.
Key words: bcl-2, mdm-2, p53, prognosis, transitional cell carcinoma, urothelial tract cancer
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