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Ki-67 MIB1 labelling index and the prognosis of primary TaT1 urothelial cell carcinoma of the bladder
  1. A Quintero1,
  2. J Alvarez-Kindelan2,
  3. R J Luque3,
  4. R Gonzalez-Campora4,
  5. M J Requena2,
  6. R Montironi5,
  7. A Lopez-Beltran6
  1. 1Biomedical Research Unit, Reina Sofia University Hospital and Cordoba University Medical School, 14004 Cordoba, Spain
  2. 2Urology Service, Reina Sofia University Hospital and Cordoba University Medical School
  3. 3Department of Pathology, University Hospitals, 23007 Jaen, Spain
  4. 4Department of Pathology, University Hospitals, 41009 Seville, Spain
  5. 5Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region (Ancona), 60020 Ancona, Italy
  6. 6Department of Pathology, Reina Sofia University Hospital and Cordoba University Medical School, 14004 Cordoba, Spain
  1. Correspondence to:
 Professor A Lopez-Beltran
 Faculty of Medicine, Avda. Menendez Pidal S/N, 14004 Cordoba, Spain; em1lobea{at}uco.es

Abstract

Aims: To evaluate whether ki-67 labelling index (LI) has independent prognostic value for survival of patients with bladder urothelial tumours graded according to the 2004 World Health Organisation classification.

Methods: Ki-67 LI was evaluated in 164 cases using the grid counting method. Non-invasive (stage Ta) tumours were: papilloma (n = 5), papillary urothelial neoplasia of low malignant potential (PUNLMP; n = 26), and low (LG; n = 34) or high grade (HG; n = 15) papillary urothelial carcinoma. Early invasive (stage T1) tumours were: LG (n = 58) and HG (n = 26) carcinoma. Statistical analysis included Fisher and χ2 tests, and mean comparisons by ANOVA and t test. Univariate and multivariate survival analyses were performed according to the Kaplan–Meier method with log rank test and Cox’s proportional hazard method.

Results: Mean ki-67 LI increased from papilloma to PUNLMP, LG, and HG in stage Ta (p<0.0001) and from LG to HG in stage T1 (p = 0.013) tumours. High tumour proliferation (>13%) was related to greater tumour size (p = 0.036), recurrence (p = 0.036), progression (p = 0.035), survival (p = 0.054), and high p53 accumulation (p = 0.015). Ki-67 LI and tumour size were independent predictors of disease free survival (DFS), but only ki-67 LI was related to progression free survival (PFS). Cancer specific overall survival (OS) was related to ki-67 LI, tumour size, and p27kip1 downregulation. Ki-67 LI was the main independent predictor of DFS (p = 0.0005), PFS (p = 0.0162), and cancer specific OS (p = 00195).

Conclusion: Tumour proliferation measured by Ki-67 LI is related to tumour recurrence, stage progression, and is an independent predictor of DFS, PFS, and cancer specific OS in TaT1 bladder urothelial cell carcinoma.

  • DFS, disease free survival
  • HG, high grade
  • ISUP, International Society of Urological Pathologists
  • LG, low grade
  • LI, labelling index
  • PFS, progression free survival
  • PUNLMP, papillary urothelial neoplasia of low malignant potential
  • OS, overall survival
  • RR, relative risk
  • WHO, World Health Organisation
  • bladder cancer
  • survival
  • prognosis
  • ki-67 MIB1
  • grade

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