Urine Detection of Survivin is a Sensitive Marker for the Noninvasive Diagnosis of Bladder Cancer

Shariat, Shahrokh F.; Casella, Roberto; Khoddami, Seyed M.; Hernández, Gina; Sulser, Tullio; Gasser, Thomas C.; Lerner, Seth P.

doi:10.1097/01.ju.0000107826.78479.90

Cited by 161 publications

(87 citation statements)

References 8 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Zhang

et al. 2006

Modern Pathology

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The caspase family proteases are key proapoptotic proteins while the inhibitor of apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other key proapoptotic proteins. Limited studies of IAPs suggested their deregulation contributed to urothelial neoplasia. However, the expression status and biologic or prognostic significance of the caspase and IAP family proteins in urothelial neoplasms is not clear. In the present study, we first systematically evaluated the expression profile of the major apoptosis regulators, including caspases (CASP3,6,7,8,9,10,and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples by immunohistochemistry. The analysis showed that survivin/ BIRC5 nuclear labeling index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker which correlated significantly with tumor grade, stage, and patient outcome. We further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well as the more classical prognosticators (stage, grade, and Ki67 index) were of prognostic significance. However, multivariate analysis by Cox proportional hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted unfavorable disease-specific survival (relative risk (RR) ¼ 6.6, 95% confidence interval ¼ 1.6-26.7, P ¼ 0.0080) as well as progression-free survival (RR ¼ 4.4, 95% confidence interval ¼ 1.3-14.6, P ¼ 0.0151). We conclude that BIRC5-N is a superior biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary bladder.

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Section: Discussionmentioning

confidence: 99%

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

Chen

Zhang

et al. 2006

Modern Pathology

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“…6 In humans, urinary levels of Survivin are significantly elevated in patients with bladder cancer compared with controls. 9,10,22 These findings together with the Survivin-related inhibition of tumor cell apoptosis 7,8,10,14,23,24,[27][28][29] and changes in gene expression 6 indicate that Survivin contributes to bladder carcinogenesis. Survivin expression was an independent predictor of disease recurrence and bladder cancer-specific mortality in patients treated with radical cystectomy.…”

Section: Discussionmentioning

confidence: 99%

“…7 In bladder cancer, urinary levels of Survivin gene activation, both at the protein and the mRNA level, have been shown to be associated with cancer presence, higher tumor grade, and advanced pathologic stage. [9][10][11] Immunohistochemical expression of Survivin was found in 78% of patients with localized bladder TCC but was absent in normal bladder urothelium. 12 There are a few conflicting reports regarding the association of Survivin expression with recurrence rates in nonmuscle-invasive bladder TCC but they do not address outcomes in patients treated with radical cystectomy.…”

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confidence: 99%

Survivin expression is associated with bladder cancer presence, stage, progression, and mortality

Shariat

Ashfaq

Karakiewicz

et al. 2007

Cancer

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136

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BACKGROUNDThe purpose was to compare the differential expression of Survivin in normal bladder tissue, bladder transitional cell carcinoma (TCC) of different stages, and to determine whether expression of Survivin is associated with TCC clinical outcomes.METHODSImmunohistochemical staining for Survivin was carried out on archival bladder specimens from 9 normal controls and 222 consecutive patients who underwent radical cystectomy and bilateral lymphadenectomy. Lymph node tissue involved with TCC from 50 of the 222 cystectomy patients was also evaluated.RESULTSSurvivin was expressed in none of the normal bladder specimens, 64% of the cystectomy specimens, and 94% of the malignant lymph nodes. Multivariable analyses performed in the cystectomy patients revealed that Survivin expression was associated with disease recurrence (P = .040), disease‐specific mortality (P = .037), and all‐cause mortality (P = .044).CONCLUSIONSThe findings of the study provide a rationale for further evaluation of Survivin and its downstream signaling pathways in bladder cancer and raise the potential for Survivin‐targeted therapy for bladder cancer. Cancer 2007. © 2007 American Cancer Society.

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“…Recently, it has been proposed as a new marker for bladder cancer detection (34 -36). Urine detection of survivin is useful for the diagnosis and prognosis in bladder carcinomas (35,36). It is correlated with decreased survival, unfavorable prognosis, and accelerated rates of recurrences in cancer therapy (37).…”

Section: Introductionmentioning

confidence: 99%

Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT

Liu

2007

Molecular Cancer Therapeutics

127

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The bioactive flavonoid baicalein has been shown to have in vitro growth-inhibitory activity in human cancer cells, although the mechanism of action is poorly understood. Baicalein (40 -80 Mmol/L for 24 h) more effectively induced cytotoxicity compared with other flavonoids (baicalin, catechin, genistein, quercetin, and rutin) in bladder cancer cells. Baicalein induced cell proliferation inhibition and apoptosis. The levels of cyclin B1 and phospho-CDC2 (Thr 161 ) were reduced, whereas the G 2 -M phases were elevated by baicalein. Treatment of CDC2 kinase or CDC25 phosphatase inhibitors augments the baicalein-induced cytotoxicity. A variety of human bladder cancer cell lines expressed survivin proteins, which were located on the mitotic phases and regulated mitotic progression. Baicalein markedly reduced survivin protein expression. Transfection of a survivin small interfering RNA diminished the level of survivin proteins and increased the baicalein-mediated cell death. Overexpression of survivin enhanced cell proliferation and resisted the baicalein-induced cytotoxicity. Interestingly, baicalein induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and AKT. SB203580, a specific p38 MAPK inhibitor, attenuated proliferation inhibition and restored the protein levels of phospho-CDC2 (Thr 161 ) and survivin in the baicalein-exposed cells; conversely, blockade of AKT activation enhanced cytotoxicity and the reduction of phospho-CDC2 (Thr 161 ) and survivin proteins.As a whole, these findings provide that the opposite role of p38 MAPK and AKT regulates CDC2 kinase and survivin and the inhibition of CDC2-survivin pathway by baicalein contributes to apoptosis and proliferation retardation in cancer cells.

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Urine Detection of Survivin is a Sensitive Marker for the Noninvasive Diagnosis of Bladder Cancer

Abstract: Urine survivin was a strong, independent predictor of the presence of bladder cancer and higher tumor grade. Urine detection of survivin is an accurate diagnostic test for bladder cancer that retains its efficiency regardless of cancer stage and grade.

Cited by 161 publications

References 8 publications

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

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

Survivin expression is associated with bladder cancer presence, stage, progression, and mortality

Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT

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