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 Journal Article


Authors: Maluf, F. C.; Cordon-Cardo, C.; Verbel, D. A.; Satagopan, J. M.; Boyle, M. G.; Herr, H.; Bajorin, D. F.
Article Title: 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
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, p 53, 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. © 2006 Oxford University Press.
Keywords: adult; cancer survival; controlled study; human tissue; protein expression; aged; middle aged; survival analysis; major clinical study; cisplatin; doxorubicin; cancer adjuvant therapy; neoadjuvant therapy; methotrexate; cancer staging; phenotype; protein bcl 2; protein protein interaction; neoplasm proteins; retrospective study; bladder cancer; protein p53; tumor marker; prediction; urinary bladder neoplasms; vinblastine; cancer invasion; molecular marker; urothelial tract cancer; survival time; correlation analysis; statistical significance; cancer cell; lymph node; staining; tumor suppressor protein p53; neoplasm invasiveness; transurethral resection; transitional cell carcinoma; proto-oncogene proteins c-bcl-2; p53; muscle metastasis; protein mdm2; proto-oncogene proteins c-mdm2; muscles; bcl-2; mdm-2
Journal Title: Annals of Oncology
Volume: 17
Issue: 11
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2006-11-01
Start Page: 1677
End Page: 1686
Language: English
DOI: 10.1093/annonc/mdl289
PUBMED: 16984978
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 15" - "Export Date: 4 June 2012" - "CODEN: ANONE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Dean Bajorin
    432 Bajorin
  2. Jaya M Satagopan
    138 Satagopan
  3. Fernando Maluf
    10 Maluf
  4. David A Verbel
    20 Verbel
  5. Harry W Herr
    417 Herr
  6. Mary G Boyle
    29 Boyle