P-cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells.
OBJECTIVE
To identify changes associated with P-cadherin expression in bladder cancer and evaluate the potential role of such events in determining the clinical outcome and cell behaviour, as the function of P-cadherin in normal epithelium is unknown, as is its potential role in neoplastic progression in different cancers.


METHODS
In all, 536 bladder tumour specimens from 408 patients were assembled in seven tissue microarrays. Paraffin sections from each array were processed for immunohistochemistry to assess the expression of P-cadherin. The expression of P-cadherin was forced using lipofectin, followed by an assessment of migration and invasion potential using standard in vitro assays.


RESULTS
The absence of P-cadherin staining was associated with muscle-invasive disease, grade 3 (P < 0.001) and nodal disease (P = 0.009). Similar results were obtained when considering cytoplasmic and unrestricted localization of P-cadherin (P < 0.001), except for nodal involvement. The group with cytoplasmic location of P-cadherin showed a shorter cancer-specific survival than the group with membrane location of P-cadherin (P = 0.03). Forced expression of P-cadherin in EJ and UM-UC-3 cells, that constitutively lack P-cadherin expression, resulted in modulation of catenin expression and enhanced migration of EJ and UM-UC-3/P-cadherin transfectants (>200%).


CONCLUSIONS
These results showed that loss of expression, cytoplasmic relocation or unrestricted tissue location of P-cadherin was associated with a poor clinical outcome and prognosis in bladder cancer. From the in vitro work it is evident that P-cadherin plays a role in regulating the migration potential of bladder carcinoma cells.
Mandeville
Jessica A
JA
Department of Urology, Lahey Clinic, Burlington, MA 01805, USA.
Silva Neto
Brasil
B
Vanni
Alex J
AJ
Smith
Gjanje L
GL
Rieger-Christ
Kimberly M
KM
Zeheb
Ron
R
Loda
Massimo
M
Libertino
John A
JA
Summerhayes
Ian C
IC
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology*; D002465:Cell Movement; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; D015820:Cadherins