Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer

J Clin Oncol. 2004 Apr 1;22(7):1242-52. doi: 10.1200/JCO.2004.09.034.

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 [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.

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, 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology
  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism*
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology
  • Catenins
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism*
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Cytoskeletal Proteins / metabolism*
  • Delta Catenin
  • Endometrial Neoplasms / epidemiology
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Norway / epidemiology
  • Phosphoproteins / metabolism*
  • Prognosis
  • Protein Array Analysis
  • Survival Rate
  • Trans-Activators / metabolism*
  • beta Catenin

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Cadherins
  • Catenins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Trans-Activators
  • beta Catenin
  • Delta Catenin
  • CTNND1 protein, human