Differences in gene expression in muscle-invasive bladder cancer: a comparison of Italian and American patients.
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.
Williams
S G
SG
Department of Urology, University of California-Davis, Sacramento, Calif, USA.
Gandour-Edwards
R
R
Deitch
A D
AD
Toscano
S
S
Fan
J J
JJ
Sternberg
C N
CN
Pansadoro
V
V
Calabrò
F
F
Rossetti
A
A
deVere White
R W
RW
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*