title: E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder.
abstract: OBJECTIVE
  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 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.
authors.affiliation: Scott Department of Urology, Baylor College of Medicine and The Methodist Hospital, Houston, Texas, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Shariat
authors.forename: S
authors.initials: S
authors.lastname: Pahlavan
authors.forename: A G
authors.initials: AG
authors.lastname: Baseman
authors.forename: R M
authors.initials: RM
authors.lastname: Brown
authors.forename: A E
authors.initials: AE
authors.lastname: Green
authors.forename: T M
authors.initials: TM
authors.lastname: Wheeler
authors.forename: S P
authors.initials: SP
authors.lastname: Lerner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015820:Cadherins / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015653:Cystectomy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D015820:Cadherins; D009363:Neoplasm Proteins