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

Abstract

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, logrank 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.

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

“…24 Another reported correlation of BIRC5 mRNA expression with tumor grade and stage (pTa-T3). 27 Yet another found no correlation of BIRC5 immunostaining with grade or stage in Ta/T1 carcinomas. 26 Reports regarding prognostic value of IAPs in urothelial carcinoma were scarce, [22][23][24]26,27 and that of caspases were lacking.…”

“…5,[7][8][9]12,13,18,20 More recently, the potential role of two IAP family members in bladder cancer was studied by a few groups. 22,24,26,27 Gazzaniga et al, 24 using RT-PCR, observed 30% positivity for BIRC5 and 23% for Livin in Ta/T1 carcinomas. Weikert et al 27 reported detection of BIRC5 mRNA in bladder cancer (100%) but not in normal urothelium.…”

“…22,24,26,27 Gazzaniga et al, 24 using RT-PCR, observed 30% positivity for BIRC5 and 23% for Livin in Ta/T1 carcinomas. Weikert et al 27 reported detection of BIRC5 mRNA in bladder cancer (100%) but not in normal urothelium. Ku et al 26 reported high BIRC5 expression (defined as 420% of tumor cells) in 58.0% Ta/T1 tumors.…”

“…Detection of BIRC5 in urine as an attractive, highly sensitive and specific marker of bladder cancer, has also been reported. 27,37,38 The expression status of other IAP family members and the caspases in Ta or T1 urothelial tumors has not been explored previously. The present study is the first to systematically evaluate expression of caspases, APAF1, SMAC, and the IAPs in Ta or T1 urothelial carcinomas.…”

“…33 Limited studies of a few of the IAP family proteins in urothelial carcinomas suggested their deregulation might contribute to urothelial neoplasia. [22][23][24]26,27 Researchers are also exploring experimental approaches targeting Survivin/BIRC5 to induce bladder cancer cell death. 34 However, systematic evaluation of the expression profile and biologic significance of these apoptosis regulators in urothelial carcinomas is lacking.…”