Prognostic Significance Of Abnormal P-Cadherin Expression In Transitional Cell Carcinoma Of The Bladder

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 15 Jun 2008 - 3:00 PDT

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ORLANDO, FL (UroToday.com) - The roles of E-cadherin and N-cadherin in bladder cancer have been investigated and are linked to the suppression or promotion of invasive potential, respectively. The objective of this study was to identify the expression profile of P-cadherin in TCC linked to clinical variables and thus define a potential role in bladder tumorigenesis.

The group from Massachusetts assembled TMAs from a total of 536 surgically resected bladder tumor specimens from 409 patients (269 non-invasive, 238 invasive, and 29 Tx). The TMAs were analyzed using immunohistochemistry. The intensity of P-cadherin staining was scored on a scale of 0-3. Cellular localization was recorded as membranous or cytoplasmic. Tisuue localization of P-cadherin in each core was recorded as basal or unrestricted. Outcome analysis was performed using Pearson's chi-square tests. Spearman's correlation coefficient was used to compare P-cadherin with the expression of other cadherin/catenin elements. Overall and cancer-specific survival analysis was restricted to the cystectomy group and Kaplan-Meier/log rank test was performed.

The absence of P-cadherin staining was associated with muscle invasive disease, grade 3 classification (p<0.001) and nodal disease (p=0.009) but not lymphovascular invasion. Similar results were recorded when considering cytoplasmic and unrestricted localization of P-cadherin (p<0.0001) with the exception of nodal involvement. A significant association was observed between cytoplasmic and unrestricted localization (R=0.266, p<0.001). There was a significant correlation between loss of expression, cytoplasmic and unrestricted localization of P-cadherin with low expression and cytoplasmic localization of plakoglobin, E-cadherin, β-catenin and p120ctn. In survival analysis, the group with the cytoplasmic localization of P-cadherin showed shorter cancer-specific survival when compared to the group displaying membrane localization of P-cadherin (p=0.003). No difference was recorded between these groups in overall survival analysis.

The investigators have demonstrated that the loss of expression, the cytoplasmic relocation or the unrestricted tissue localization of P-cadherin, are associated with poor clinical outcome and prognosis in bladder cancer.

Presented by Gjanje L Smith, MD, et al., at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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