E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder

Abstract

Objectives. The clinical course of carcinoma in situ (CIS) of the bladder is highly variable. Our objective in this study was to describe E-cadherin expression patterns in CIS with and without papillary disease and to determine whether altered E-cadherin expression is associated with disease progression and survival in patients with CIS of the bladder. Methods. Tumor specimens from 53 patients who had CIS in the absence of muscle-invasive carcinoma on bladder biopsy were identified. Formalin-fixed paraffin sections were processed using a hot citric acid antigen retrieval method, followed by immunostaining with anti-E-cadherin monoclonal antibody. Expression patterns were evaluated in a blinded fashion and scored as normal and abnormal, which included absent and various degrees of heterogeneous immunostaining. Outcomes analyzed were recurrence, progression, and survival. Results. Loss of normal membrane E-cadherin immunoreactivity was found in 17 patients (32%). At a median follow-up of 131 months, abnormal E-cadherin expression was significantly associated with disease recurrence ( P = 0.0087), disease progression ( P = 0.0003), and bladder cancer-specific survival ( P = 0.0285). In multivariate analyses, E-cadherin expression was independently associated with disease recurrence ( P = 0.019, 95% confidence interval [CI] 1.342 to 5.940), disease progression ( P = 0.002, 95% CI 2.049 to 17.989), and bladder cancer-specific survival ( P = 0.025, 95% CI 1.179 to 10.432). Conclusions. Loss of E-cadherin expression in patients with CIS with and without papillary disease of the bladder predicts disease recurrence, disease progression, and bladder cancer-specific death. CIS with and without papillary disease associated with abnormal E-cadherin expression may represent a biologically more aggressive cancer, requiring early definitive therapy. This hypothesis should be evaluated in larger studies and prospective clinical trials.