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.


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.
Silva Neto
Brasil
B
Cell and Molecular Biology Laboratory, R.E. Wise M.D. Research and Education Institute, Department of Urology, Lahey Clinic, Burlington, MA 01805, USA.
Smith
Gjanje L
GL
Mandeville
Jessica A
JA
Vanni
Alex J
AJ
Wotkowicz
Chad
C
Rieger-Christ
Kimberly M
KM
Baumgart
Egbert
E
Jacobs
Micah A
MA
Cohen
Michael S
MS
Zeheb
Ron
R
Loda
Massimo
M
Libertino
John A
JA
Summerhayes
Ian C
IC
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015653:Cystectomy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering; D012307:Risk Factors; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000095002:Delta Catenin
D014408:Biomarkers, Tumor; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D000095002:Delta Catenin; C000722347:CTNND1 protein, human