title: MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder: clinical significance and comparison with other prognostic factors.
abstract: BACKGROUND
  Staging and grading of transitional cell carcinoma of the bladder are generally viewed as indicators of prognosis and form the basis of therapy, but they do not predict outcome accurately. This study was designed to evaluate the value for predicting recurrence, progression, and survival of proliferation fraction in transitional cell carcinoma of the bladder determined by immunostaining of histopathologic specimens with the monoclonal antigen MIB-1.
  
  
  METHODS
  In a prospectively followed group of 301 patients with transitional cell carcinoma of the bladder, formalin fixed tumor specimens were immunostained and the MIB-1 labeling index was determined. Crude survival, progression free survival, and recurrence free survival (for patients with Ta and T1 tumors) were assessed in univariate and multivariate analysis according to stage, grade, mitotic index of the tumor, and patient age. The median value of continuous variables was used as a cutoff point in statistical analysis.
  
  
  RESULTS
  In univariate analysis there was a strong association between all included factors and crude survival, progression free survival, and recurrence free survival with a median follow-up period of 60 months. In multivariate analysis, crude survival and progression free survival were determined by stage (P = 0.0001) and age (P = 0.0001). Recurrence free survival for patients with Ta and T1 tumors was determined by MIB-1 labeling index (P = 0.0317), mitotic index (P = 0.0229), and age (P = 0.0001).
  
  
  CONCLUSIONS
  MIB-1 immunostaining in transitional cell carcinoma of the bladder correlated well with grade, stage, and clinical outcome. In multivariate analysis, proliferation fraction had prognostic value in predicting recurrence free survival for patients with Ta and T1 tumors, whereas stage and age appeared to be predictors of progression free survival.
authors.affiliation: Department of Surgery, Stichting Ziekenhuizen, Noord-Limburg, Venlo, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: R F
authors.initials: RF
authors.lastname: Schapers
authors.forename: M L
authors.initials: ML
authors.lastname: Janssen-Heijnen
authors.forename: A W
authors.initials: AW
authors.lastname: Smeets
authors.forename: R P
authors.initials: RP
authors.lastname: Pauwels
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins