Prognostic significance of altered p120^ctn expression in bladder cancer

OBJECTIVE: To identify the frequency of change in the expression and localization of p120^ctn in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120^ctn in the migratory and invasive behaviour of bladder carcinoma cells. MATERIALS AND METHODS: In all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2-T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120^ctn immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120^ctn was achieved using small-interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays. RESULTS: The expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non-membranous localization of p120 ^ctn correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN-positive disease (P = 0.02). A low expression level of p120^ctn was linked to a poor outcome in cancer-specific survival analysis. Knockdown of p120^ctn using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells. CONCLUSIONS: Our findings suggest that p120 ^ctn acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells.