Prognostic Impact of Alterations in P-Cadherin Expression and Related Cell Adhesion Markers in Endometrial Cancer

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Abstract
Purpose: Reduced tumor cell adhesion is associated with invasive growth and unfavorable prognosis. In endometrial carcinoma, the prognostic impact of adhesion markers (E-cadherin, beta-catenin [β-catenin], P-cadherin, and p120ctn) is partly unknown. We wanted to examine the expression pattern and prognostic value of these molecules in a population-based series of endometrial carcinoma patients. Patients and Methods: All patients diagnosed with endometrial carcinoma between 1981 and 1990 in Hordaland County, Norway, were included. Paraffin-embedded tumor tissue was available for 96% of the patients (n = 286), and was studied immunohistochemically for expression of E-cadherin, β-catenin, P-cadherin, and p120ctn. The tissue microarray technique was used for P-cadherin and p120ctn. Median follow-up time for survivors was 9 years (range, 4 to 16 years) and follow-up was complete. Results: Pathologic expression of P-cadherin, E-cadherin, and β-catenin was associated with a majority of the clinicopathologic variables. In univariate survival analyses, all adhesion markers influenced survival significantly (P < .05). Tumors with pathologic expression of both E-cadherin (low expression) and P-cadherin (high expression; 19%), and β-catenin (low expression) and P-cadherin (high expression; 16%), had significantly reduced survival compared with the remaining samples (P < .001 for both). In multivariate models, all markers except E-cadherin showed independent prognostic significance in addition to the traditional tumor features. Conclusion: Differential expression of P-cadherin and β-catenin seems to be important in endometrial carcinoma and is associated with aggressive subgroups. Our findings also indicate that a shift from E-cadherin to P-cadherin expression (cadherin switch) is an important prognostic feature in these tumors.

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