title: Differences in gene expression in muscle-invasive bladder cancer: a comparison of Italian and American patients.
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+/p21- 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.
authors: Department of Urology, University of California-Davis, Sacramento, Calif, USA.
authors: S G
authors: SG
authors: Williams
authors: R
authors: R
authors: Gandour-Edwards
authors: A D
authors: AD
authors: Deitch
authors: S
authors: S
authors: Toscano
authors: J J
authors: JJ
authors: Fan
authors: C N
authors: CN
authors: Sternberg
authors: V
authors: V
authors: Pansadoro
authors: F
authors: F
authors: Calabrò
authors: A
authors: A
authors: Rossetti
authors: R W
authors: RW
authors: deVere White
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007558:Italy; D008297:Male; D015999:Multivariate Analysis; D009130:Muscle, Smooth; D009361:Neoplasm Invasiveness; D014481:United States; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*