Protein Expression Patterns of Ezrin Are Predictors of Progression in T1G3 Bladder Tumours Treated with Nonmaintenance Bacillus Calmette-Guérin

Abstract

BackgroundBacillus Calmette-Guérin (BCG) is a standard treatment for reducing tumour recurrence and delaying progression of high-risk, non–muscle-invasive bladder tumours. However, it is not clear yet which patients are more likely to be responders to BCG. ObjectiveTo evaluate the role of ezrin expression in bladder cancer (BCa) progression in T1G3 bladder tumours treated with BCG. Design, setting, and participantsEzrin protein expression patterns were analysed on tumour specimens belonging to 92 patients with T1G3 non–muscle-invasive BCa undergoing nonmaintenance BCG treatment. Re-resection was not performed. The median follow-up was 90.5 mo (range: 3.0–173.0). A specific tissue array was created containing three representative cores of each of the tumour specimens belonging to these patients. MeasurementsEzrin protein expression patterns were assessed by immunohistochemistry on this tissue array. Proliferation rates were assessed by means of Ki67 staining. Recurrence, progression into muscle-invasive tumours, and disease-specific overall survival (OS) rates were analysed using univariate and multivariate tests. Results and limitationsAmong the 92 patients analysed, 40 recurred (43.5%), 17 progressed (18.5%), and 14 died of the disease (15.2%). Log-rank survival analyses revealed that an ezrin membrane expression <20% was significantly associated with increased progression (p=0.009) and shorter disease-specific OS (p=0.006). Multivariate analyses showed that ezrin was an independent prognostic marker of progression (p=0.031) and disease-specific survival (p=0.035). Interestingly, the low ezrin membrane expression correlated with high proliferation rates (p=0.033). ConclusionsImmunohistochemistry analyses revealed that the membrane expression of ezrin is associated with the clinical outcome of patients with T1G3 tumours undergoing BCG treatment. Protein expression patterns of ezrin were associated with tumour progression in T1G3 disease. The differential expression of ezrin distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach.