The prognostic value of cadherin switch in bladder cancer.
Loss of E-cadherin expression and gain of N-cadherin expression ('cadherin switch') is shown to be characteristic in epithelial to mesenchymal transition (EMT), a mechanism associated with cancer progression. Furthermore, the prognostic role of P-cadherin in different cancers is controversial. The aim of this study was to evaluate the prognostic significance of 'cadherin switch' on the gene expression level in bladder cancer. Frozen tissue samples of 181 bladder cancer patients and 7 control individuals were analyzed by quantitative real-time PCR. Kaplan-Meier log-rank test and Cox univariate and multivariate analysis were performed to assess the prognostic relevance of gene expression of E-, N- and P-cadherin. Cox univariate analysis revealed that the decrease of E-cadherin and the gain of N-cadherin gene expression are risk factors for cancer-related death (P=0.087, P=0.005, respectively). Fourteen percent (13/92) of muscle-invasive bladder cancers were N-cadherin- negative. These patients had a significantly poorer prognosis than those with N-cadherin-positive muscle-invasive tumors (P=0.024). P-cadherin gene expression proved to be a significant independent prognostic factor for both cancer-specific and recurrence-free survival (P=0.011, P=0.036). The characteristic 'cadherin switch' between low- and high-stage tumors that we observed and the prognostic significance of E-, N- and P-cadherin suggests the importance of these markers in bladder cancer progression. The poor patient prognosis in N-cadherin-negative muscle-invasive tumors indicates an alternative, N-cadherin-independent way in bladder cancer progression.
Jäger
Tobias
T
Department of Urology, University of Duisburg-Essen, 45147 Essen, Germany.
Becker
Markus
M
Eisenhardt
Andreas
A
Tilki
Derya
D
Tötsch
Martin
M
Schmid
Kurt W
KW
Romics
Imre
I
Rübben
Herbert
H
Ergün
Süleyman
S
Szarvas
Tibor
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality
D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger