Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors.
OBJECTIVE
Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determined the occurrence and clinical significance of these events in a series of bladder carcinomas.


METHODS
Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, beta-catenin, N-cadherin, and vimentin.


RESULTS
Pathologic expression of E-cadherin, beta-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and beta-catenin (P = 0.02) significantly influenced survival.


CONCLUSIONS
The putative markers of EMT defined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors.
Baumgart
Egbert
E
Cell and Molecular Biology Laboratory, RE Wise MD Research and Education Institute, Department of Urology, Lahey Clinic, Burlington, MA 01805, USA.
Cohen
Michael S
MS
Silva Neto
Brasil
B
Jacobs
Micah A
MA
Wotkowicz
Chad
C
Rieger-Christ
Kimberly M
KM
Biolo
Andreia
A
Zeheb
Ron
R
Loda
Massimo
M
Libertino
John A
JA
Summerhayes
Ian C
IC
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D015820:Cadherins; D051177:Catenins