High Expression of karyopherin-α2 Defines Poor Prognosis in Non-Muscle-Invasive Bladder Cancer and in Patients With Invasive Bladder Cancer Undergoing Radical Cystectomy

Eur Urol. 2011 May;59(5):841-8. doi: 10.1016/j.eururo.2011.01.048. Epub 2011 Feb 16.

Abstract

Background: Conventional clinicopathologic risk factors have failed to accurately predict the prognosis of patients with bladder cancer (BC).

Objective: To evaluate karyopherin-α2 (KPNA2) expression as a progression marker in patients with non-muscle-invasive BC (NMIBC) treated by conservative methods and as a prognostic marker in patients with invasive BC undergoing radical cystectomy (RC).

Design, setting, and participants: Two different tissue microarrays were constructed, one with 234 primary Ta/T1 tumours from patients treated by transurethral resection of the bladder and one with 377 tumours from RC patients.

Intervention: KPNA2 expression based on immunohistochemistry.

Measurements: Risk of progression of Ta/T1 patients to muscle-invasive BC was estimated in clinical follow-up to progression or a minimum of 53 mo. Risk of recurrent disease and death following RC was estimated in clinical follow-up of a minimum of 24 mo in patients alive.

Results and limitations: A high KPNA2 expression in Ta/T1 patients was significantly correlated with a higher risk of progression that was independent of conventional risk factors in multivariate analysis. In patients undergoing RC, a high KPNA2 expression was an independent predictor of poor prognosis. A high KPNA2 expression was correlated with a higher risk of visceral metastasis rather than lymphatic spread.

Conclusions: KPNA2 expression is a marker for progression of NMIBC and a prognostic marker in patients undergoing RC.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cystectomy* / adverse effects
  • Cystectomy* / mortality
  • Denmark
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Survival Rate
  • Time Factors
  • Tissue Array Analysis
  • Transfection
  • Treatment Outcome
  • Up-Regulation
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / secondary
  • Urinary Bladder Neoplasms / surgery*
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism*

Substances

  • Biomarkers, Tumor
  • KPNA2 protein, human
  • alpha Karyopherins