Quantitative analysis of survivin mRNA expression in urine and tumor tissue of bladder cancer patients and its potential relevance for disease detection and prognosis



Suppression of apoptosis may favor the onset and progression of cancer. Survivin is an inhibitor of apoptosis that has been suggested as a novel diagnostic/prognostic marker of bladder cancer. In this study, survivin mRNA expression was measured by a sensitive real-time PCR assay in tumor tissue and urine from bladder cancer patients and assessed for its potential diagnostic and prognostic relevance. Specimens from 53 patients with bladder transitional cell carcinoma (TCC) were analyzed, the controls being normal urothelial tissues (n = 14) and urine from benign disease patients (n = 22) and healthy individuals (n = 14). Survivin transcripts were commonly detected in tumor tissues, but not in normal urothelium, and increasing mRNA levels correlate with progressing pathologic stage (p = 0.001) and grade categories (p < 0.004). Higher levels of expression were associated with a reduced time to recurrence in noninvasive TCCs (p = 0.027, log-rank test) and a trend toward shorter disease-free survival in muscle-invasive tumors (p = 0.067). Urinary survivin analysis detects TCC with higher sensitivity (68.6%) and equal specificity (100%) when compared with cytology (31.4% and 97.1%). Our results indicate that tissue levels of survivin mRNA predict disease-free survival in noninvasive TCC and may have a role in bladder cancer progression. When analyzed by RT-PCR in urine, survivin is a highly specific biomarker for TCC detection. © 2005 Wiley-Liss, Inc.