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

Objectives. The clinical course of carcinoma in situ (CIS) of the bladder i s highly variable. Our objective in this study was to describe E-cadherin e xpression patterns in CIS with and without papillary disease and to determi ne whether altered E-cadherin expression is associated with disease progres sion and survival in patients with CIS of the bladder. Methods. Tumor specimens from 53 patients who had CIS in the absence of mus cle-invasive carcinoma on bladder biopsy were identified. Formalin-fixed pa raffin sections were processed using a hot citric acid antigen retrieval me thod, followed by immunostaining with anti-E-cadherin monoclonal antibody. Expression patterns were evaluated in a blinded fashion and scored as norma l and abnormal, which included absent and various degrees of heterogeneous immunostaining. Outcomes analyzed were recurrence, progression, and surviva l. Results, Loss of normal membrane E-cadherin immunoreactivity was found in 1 7 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 independen tly 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 17.98 9), 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 wi thout papillary disease of the bladder predicts disease recurrence, disease progression, and bladder cancer-specific death. CIS with and without papil lary disease associated with abnormal E-cadherin expression may represent a biologically more aggressive cancer, requiring early definitive therapy. T his hypothesis should be evaluated in larger studies and prospective clinic al trials. UROLOGY 57: 60-65, 2001. (C) 2001, Elsevier Science Inc.