title: Ki-67 is an independent indicator in non-muscle invasive bladder cancer (NMIBC); combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC.
abstract: OBJECTIVE
  To prove the predicting role of Ki-67 expression and to demonstrate that the combination of European Organization for Research and Treatment of Cancer (EORTC) risk scores and Ki-67 staining status could improve the risk stratification in a large series of patients with non-muscle invasive bladder cancer (NMIBC).
  
  
  METHODS
  From October 2002 to July 2010, in our cohort, 332 patients who were treated with transurethral resection of the bladder tumor were diagnosed with NMIBC by histopathologic analysis. Two experienced uropathologists rereviewed the slides. The EORTC risk scores for recurrence and progression were determined. Ki-67 expression was evaluated using immunohistochemical studies and scored for intensity and area of staining. We correlated Ki-67 expression scores with clinical and pathologic variables. We evaluated the prognosis role of EORTC risk scores, Ki-67 staining, and their combination on tumor recurrence-free survival and progression-free survival (PFS) by univariate analysis, multivariate analysis, and Kaplan-Meier survival curves.
  
  
  RESULTS
  With a median follow-up of 47 (range, 2-124) months, 119 patients (35.8%) had tumor recurrence and 40 patients (12%) had tumor progression. Ki-67 positivity (Ki-67>25%) was reported in 108 tumors (32.5%), and it was significantly associated with high EORTC risk scores for both tumor recurrence and progression. In univariate analysis, multifocality, tumor size, tumor stage, tumor grade, and Ki-67 staining correlated with recurrence-free survival, whereas tumor size, tumor stage, tumor grade, concomitant CIS, and Ki-67 staining correlated with PFS. In multivariable analysis, Ki-67 expression was an independent risk factor for predicting tumor recurrence (hazard ratio, 2.14; P<0.0001) and progression (hazard ratio: 2.97, P = 0.004). Kaplan-Meier curves showed that combining EORTC risk scores and Ki-67 staining led to more accurate prediction for tumor recurrence and progression (log-rank test; P<0.0001).
  
  
  CONCLUSIONS
  Ki-67 positivity is prognostic for predicting tumor recurrence and progression. Combination of EORTC risk scores with Ki-67 expression could improve the risk stratification for both recurrence and progression in NMIBC.
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Xia
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Urology, Fudan University, Shanghai, China. Electronic address: xiaguowei@fudan.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Urology, Fudan University, Shanghai, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Qiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018450:Disease Progression; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: EORTC; Immunohistochemistry; Ki-67; Non–muscle invasive bladder cancer; Prognosis