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

Abstract

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 [beta-catenin], P-cadherin, and p120(ctn)) 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. 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, beta-catenin, P-cadherin, and p120(ctn). The tissue microarray technique was used for P-cadherin and p120(ctn). Median follow-up time for survivors was 9 years (range, 4 to 16 years) and follow-up was complete. Pathologic expression of P-cadherin, E-cadherin, and beta-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 beta-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. Differential expression of P-cadherin and beta-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.