NE-AUA 2006 Annual Meeting, September 28 - 30, 2006, The Westin Hotel & Rhode Island Convention Center Providence, Rhode Island
Back to Scientific Program
Back to Annual Meeting
Identification of the Occurrence and Clinical Significance of Epithelial to Mesenchymal Transition in Bladder Tumors In Vivo
Egbert D. Baumgart, MD1, Michael S. Cohen, MD1, Micah A. Jacobs, MD1, Chad Wotkowicz, MD1, Brasil Neto, MD2, Kimberly M. Rieger-Christ, PhD2, John A. Libertino, MD1, Ian C. Summerhayes, PhD2.
1Lahey Clinic, Burlington, MA, USA, 2Cell and Molecular Biology Laboratory, R.E. Wise M.D. Research and Education Institute, Burlington, MA,

Objective: Epithelial to mesenchymal transition (EMT) in tumors is reported as an important determinant in tumor progression indicative of the acquisition of a more aggressive phenotype. The phenotypic changes commonly associated with EMT have been characterized as loss of expression of the epithelial marker E-cadherin along with novel expression of the mesenchymal proteins vimentin and N-cadherin. Such events have been identified mainly in in vitro models of EMT. The goal of this study was to establish EMT in bladder tumorigenesis in vivo and to investigate the role of plakoglobin in this process. In addition, we proposed to assess the value of individual and combined parameters of change underlying EMT in predicting bladder tumor progression.
Materials and Methods: A total of 358 superficial tumor specimens (Ta/Tis) from 264 patients and 459 invasive tumor specimens (T1-T4) from 303 patients were assembled in ten tissue microarrays (TMA). Immunoreactivity was scored on a scale of 0-3 for E-cadherin and plakoglobin and 0 or 1 for N-cadherin and vimentin. Cellular localization of proteins was recorded as membranous, cytoplasmic or nuclear. Outcome analysis (pathological stage, grade, and lymphovascular invasion) was performed using the Pearson Chi-Square test and logistic regression.
Results: In univariate analysis, reduced or loss of expression of E-cadherin and plakoglobin, in addition to non-membranous relocation, were significantly correlated with stage progression, high-grade disease, and lymphovascular invasion. Novel expression of vimentin correlated with late-stage and high-grade disease while novel expression of N-cadherin was not correlated with any outcome parameter.
Proteins were also analyzed in reference to one another by multivariate logistic regression. Plakoglobin loss, vimentin expression, and non-membranous relocation of E-cadherin and plakoglobin were correlated with late-stage and high-grade tumors. Only the loss of E-cadherin or its relocalization was independently significant for lymphovascular invasion.
Conclusion: Phenotypic changes linked to EMT occur in bladder tumorigenesis in vivo. For prediction of aggressive disease, quantitative changes in plakoglobin and vimentin expression as well as qualitative changes in E-cadherin expression represented the variables of significance in multivariate analysis.

 

T-stage progression

High Grade

Lymphovascular Invasion

Univariate

Multivariate

Univariate

Multivariate

Univariate

Multivariate

E-cad loss

<0.001

N.S.

<0.001

N.S.

< 0.001

N.S.

Plakoglobin loss

<0.001

<0.001/4.34*

<0.001

<0.001/3.55*

<0.001

N.S.

Vimentin expression

<0.001

<0.001/2.58*

<0.001

<0.001/4.45*

N.S.

N.S.

N-cad expression

N.S.

N.S.

N.S.

N.S.

N.S.

N.S.

E-cad
m->c/n

<0.001

<0.05/1.82*

<0.001

<0.001/2.74*

<0.001

<0.001/2.75*

Plakoglobin
m->c

<0.001

<0.001/2.69*

<0.001

<0.001; 4.55

N.S.

N.S.

N.S.=not significant
*Significance/Odds Ratio

m=membranous
c=cytoplasmic
n=nuclear

 

 

 

 

 


Back to Scientific Program
Back to Annual Meeting