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-inv asive bladder cancers of two cohorts of patients having different survival rates. An Italian group treated by transurethral resection of the bladder t umor (TURBT) and neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) followed by TUR BT, partial cystectomy or radical cystectomy (75% 3-year survival) was com pa red to an American coh ort treated by radical cystectomy (51% 3-year survival). Methods: Immunohistochemistry was used to examine the protein expression le vels of three genes that act at the G1/S cell cycle checkpoint, p53, p21/wa f-1/cip(1) (a downstream effector gene in the p53 pathway) and Rb, plus a m ajor 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 bivar iate analysis, 72% of Italian tumors were immunopositive for both p53 and p 21 (p53+/p27+) vs. 49% for the American tumors. The subset of Italian patie nts with p53+/p21+ tumors were more frequently disease-free (stage pT0) fol lowing chemotherapy and were less likely to fail therapy than those with p5 3+/p21- tumors (p = 0.0357). Loss of Rb staining was associated with a decr eased 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 patie nts with p53+/p21+ tumors had significantly lower recurrence rates after TU RBT 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. Copyright (C) 2001 S. Karger AG, Basel.