This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baumgart, E. Articles by Summerhayes, I. C. Search for Related Content PubMed PubMed Citation Articles by Baumgart, E. Articles by Summerhayes, I. C.

Identification and Prognostic Significance of an Epithelial-Mesenchymal Transition Expression Profile in Human Bladder Tumors

Authors' Affiliations: ¹ Cell and Molecular Biology Laboratory, R.E. Wise M.D. Research and Education Institute; Departments of ² Urology and ³ Pathology, Lahey Clinic, Burlington, Massachusetts; ⁴ Department of Internal Medicine and Cardiology, Hospital De Clinicas de Porto Alegre, Porto Alegre, Brazil; and ⁵ Department of Pathology, Dana-Farber Cancer Center, Boston, Massachusetts

Requests for reprints: Ian C. Summerhayes, Cell and Molecular Biology Laboratory, Robert E. Wise M.D. Research and Education Institute, Lahey Clinic, 31 Mall Road, Burlington, MA 01805. Phone: 781-744-2990; Fax: 781-744-2984; E-mail: Ian.C.Summerhayes{at}lahey.org.

Purpose: 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.

Experimental Design: 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, ß-catenin, N-cadherin, and vimentin.

Results: Pathologic expression of E-cadherin, ß-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 ß-catenin (P = 0.02) significantly influenced survival.

Conclusion: 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.

This article has been cited by other articles:

				N. Kobayashi, K. Suzuki, H. Shibuya, T. Sato, I. Aoki, and Y. Nagashima Renal Collecting Duct Carcinoma in a Dog Vet. Pathol., July 1, 2008; 45(4): 489 - 494. [Abstract] [Full Text] [PDF]

				P. C. Black, G. A. Brown, T. Inamoto, M. Shrader, A. Arora, A. O. Siefker-Radtke, L. Adam, D. Theodorescu, X. Wu, M. F. Munsell, et al. Sensitivity to Epidermal Growth Factor Receptor Inhibitor Requires E-Cadherin Expression in Urothelial Carcinoma Cells Clin. Cancer Res., March 1, 2008; 14(5): 1478 - 1486. [Abstract] [Full Text] [PDF]