Differences in gene expression in muscle-invasive bladder cancer: A comparison of Italian and American patients

S. G. Williams, Regina F Gandour-Edwards, A. D. Deitch, S. Toscano, J. J. Fan, C. N. Sternberg, V. Pansadoro, F. Calabrò, A. Rossetti, Ralph W deVere White

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Objective: To seek differences in gene expression in the primary muscle-invasive bladder cancers of two cohorts of patients having different survival rates. An Italian group treated by transurethral resection of the bladder tumor (TURBT) and neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) followed by TURBT, partial cystectomy or radical cystectomy (75% 3-year survival) was compared to an American cohort treated by radical cystectomy (51% 3-year survival). Methods: Immunohistochemistry was used to examine the protein expression levels of three genes that act at the G1/S cell cycle checkpoint, p53, p21/waf-1/cip1 (a downstream effector gene in the p53 pathway) and Rb, plus a major inhibitor of apoptosis, Bcl-2. Results: For the bladder cancers of the Italian patient cohort, there was a significantly higher rate of p53 immunopositivity (93 vs. 63%, p = 0.002) and a significantly lower rate of Rb loss (25 vs. 54%, p = 0.009). In bivariate analysis, 72% of Italian tumors were immunopositive for both p53 and p21 (p53+/p21+) vs. 49% for the American tumors. The subset of Italian patients with p53+/p21+ tumors were more frequently disease-free (stage pT0) following chemotherapy and were less likely to fail therapy than those with p53+/p2-tumors (p = 0.0357). Loss of Rb staining was associated with a decreased 5-year survival in the Italian, but not in the American patients. Conclusions: (1) Significant differences in the expression of the p53, p21 and Rb genes were found between the 2 groups of patients. (2) Italian patients with p53+/p21+ tumors had significantly lower recurrence rates after TURBT and chemotherapy than those having p53+/p21- tumors. (3) Absence of p21 immunopositivity in the Italian tumors may identify alterations in the p53 pathway that predict poor outcome.

Original languageEnglish (US)
Pages (from-to)430-437
Number of pages8
JournalEuropean Urology
Volume39
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Bladder neoplasm
  • p21 genes
  • p53 genes
  • Retinoblastoma genes
  • Survival rate

ASJC Scopus subject areas

  • Urology

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    Williams, S. G., Gandour-Edwards, R. F., Deitch, A. D., Toscano, S., Fan, J. J., Sternberg, C. N., Pansadoro, V., Calabrò, F., Rossetti, A., & deVere White, R. W. (2001). Differences in gene expression in muscle-invasive bladder cancer: A comparison of Italian and American patients. European Urology, 39(4), 430-437. https://doi.org/10.1159/000052481