ORIGINAL ARTICLE

Ki-67 MIB1 labelling index and the prognosis of primary TaT1 urothelial cell carcinoma of the bladder

A Quintero¹, J Alvarez-Kindelan², R J Luque³, R Gonzalez-Campora⁴, M J Requena², R Montironi⁵, A Lopez-Beltran⁶

¹ Biomedical Research Unit, Reina Sofia University Hospital and Cordoba University Medical School, 14004 Cordoba, Spain
² Urology Service, Reina Sofia University Hospital and Cordoba University Medical School
³ Department of Pathology, University Hospitals, 23007 Jaen, Spain
⁴ Department of Pathology, University Hospitals, 41009 Seville, Spain
⁵ Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region (Ancona), 60020 Ancona, Italy
⁶ Department of Pathology, Reina Sofia University Hospital and Cordoba University Medical School, 14004 Cordoba, Spain

Correspondence to:
Correspondence to:
Professor A Lopez-Beltran
Faculty of Medicine, Avda. Menendez Pidal S/N, 14004 Cordoba, Spain; em1lobea{at}uco.es

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 ² 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.

Abbreviations: 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

Keywords: bladder cancer; survival; prognosis; ki-67 MIB1; grade

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