Prognostic significance of altered p120 ctn expression in bladder cancer

• Published in: BJU international Vol. 101; no. 6; pp. 746 - 752
• Main Authors: Silva Neto, Brasil, Smith, Gjanje L, Mandeville, Jessica A, Vanni, Alex J, Wotkowicz, Chad, Rieger-Christ, Kimberly M, Baumgart, Egbert, Jacobs, Micah A, Cohen, Michael S, Zeheb, Ron, Loda, Massimo, Libertino, John A, Summerhayes, Ian C
• Format: Journal Article
• Language: English
• Published: England 01.03.2008
• Subjects: Biomarkers, Tumor - metabolism; Blotting, Western; Carcinoma, Transitional Cell - mortality; Carcinoma, Transitional Cell - pathology; Carcinoma, Transitional Cell - surgery; Catenins; Cell Adhesion Molecules - metabolism; Cystectomy - methods; Humans; Immunohistochemistry; Lymphatic Metastasis; Microarray Analysis; Neoplasm Invasiveness; Neoplasm Staging; Phosphoproteins - metabolism; Prognosis; Risk Factors; RNA, Small Interfering; Survival Analysis; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - surgery
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2007.07264.x

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. 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. 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. 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.