High expression of karyopherin-α2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy

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.