Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi‐institutional study

Abstract

Study Type – Prognosis (multi‐centre cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? More men than women develop bladder cancer (BC) but reasons why are unclear. Recent findings have implicated androgens, androgen receptors (AR) and AR expression in BC. Previous studies showed that a significant loss of AR expression was associated with aggressive BC. However, these results have been gathered on limited series of patients. We analyzed the expression of AR in BC and its correlation with gender, grade, stage and clinical outcome on a large multi‐institutional (Toronto/Dallas) cohort. In contrast to previous reports, our data do not suggest that loss of AR expression is gender‐related nor associated with invasive BC. In fact, in this large cohort, we showed that AR positivity is actually uncommon in BC, that there are no differences in expression among high and low grade tumours and no statistically significant differences between muscle‐invasive AR‐positive and AR‐negative cases in time to death, or time to recurrence. OBJECTIVE • To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC. PATIENTS AND METHODS • A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non‐muscle‐invasive UBC (n= 167) and muscle‐invasive UBC (n= 305) were accrued and immunohistochemical staining for AR was performed. • We used bright‐field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring. • Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA. RESULTS • The AR were positively expressed in 61/472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed. • Only 9.0% of non‐muscle‐invasive BC expressed the AR compared with 15.1% of muscle‐invasive tumours (P= 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours. • There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR‐positive and AR‐negative cases. CONCLUSION • In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender‐related nor is it associated with invasive BC.