European Urology

European Urology

Volume 48, issue 1, pages 1-178, July 2005

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Urinary Levels of Soluble E-Cadherin in the Detection of Transitional Cell Carcinoma of the Urinary Bladder

Shahrokh F. Shariat, Kazumasa Matsumoto, Roberto Casella, Weiguo Jian, Seth P. Lerner.

Accepted 16 February 2005, Published online 14 March 2005, pages 69 - 76


Abstract

Objective:

To test the hypothesis that elevated urinary levels of soluble E-cadherin (sE-cadherin) would aid in the detection of transitional cell carcinoma (TCC) of the urinary bladder.

Methods:

We performed sE-cadherin staining of one murine (MBT2) and four human (RT4, 5637, T24, and TCCSUP) bladder cancer cell lines. sE-cadherin levels were also determined in voided urine of 188 consecutive subjects at risk for TCC recurrence, 31 patients with other uro-pathologic conditions, and 10 healthy subjects using a commercially-available ELISA kit. sE-cadherin was analyzed continuously and categorically on the basis of its median distribution.

Results:

Moderately and poorly differentiated bladder cancer cell lines had decreased cellular E-cadherin expression, whereas RT4, a well differentiated cell line, had preserved expression. All cell lines had measurable sE-cadherin levels in their conditioned media. The area under the ROC curve of sE-cadherin for the detection of TCC was 0.719 (95%CI, 0.637–0.801; p < 0.001). Higher levels of sE-cadherin were associated with positive cytology results (p = 0.012) and muscle invasive tumor stage (p = 0.009). Urinary sE-cadherin was more sensitive, but less specific than urinary cytology for the detection of bladder TCC. In a multivariable logistic regression analysis, higher sE-cadherin and positive cytology were both associated with an increased risk of bladder TCC (p = 0.048 and p < 0.001, respectively). Combination of cytology and sE-cadherin allowed categorization of patients into three significantly different risk groups for bladder cancer. Adjustment of sE-cadherin for urinary creatinine levels did not affect any of the outcomes.

Conclusions:

Urinary level of sE-cadherin may add information to cytology in the detection of bladder TCC.

Keywords: Bladder cancer, Urine biomarker, Diagnosis, E-cadherin.


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