title: Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease.
abstract: OBJECTIVE
  To determine the association of the cell proliferative marker Ki-67 with pathologic features and disease prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder.
  
  
  METHODS
  Immunohistochemical staining for Ki-67 was done on serial cuts from tissue microarrays containing cystectomy specimens from 9 patients without bladder cancer and 226 consecutive patients with bladder TCC. We also assessed malignant lymph nodes from 50 of the 226 cystectomy patients.
  
  
  RESULTS
  Ki-67 expression was increased in 42.5% cystectomy specimens and in 54% metastatic lymph nodes. In contrast, it was absent in all nine benign cystectomy specimens. Ki-67 overexpression was associated with advanced pathologic stage, higher grade, lymphovascular invasion, and metastases to lymph nodes (P = 0.001, 0.040, 0.031, and 0.036, respectively). In multivariate analyses, pathologic stage and lymph node metastases were independent predictors of disease recurrence and bladder cancer-specific mortality. In the subgroup of patients with organ-confined disease (<pT(3) N(0); n = 91), excluding patients who received neoadjuvant or adjuvant chemotherapy, Ki-67 status was an independent predictor of both disease recurrence (risk ratio, 7.591; P = 0.001) and bladder cancer-specific mortality (risk ratio, 4.045; P = 0.041).
  
  
  CONCLUSIONS
  Ki-67 overexpression is associated with features of aggressive bladder TCC and adds independent prognostic information to standard pathologic features for prediction of clinical outcome after radical cystectomy.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000502:physiology; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015653:Cystectomy / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000601:surgery*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen