title: Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, the Gade Institute, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stefansson
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009664:Norway / Q000453:epidemiology; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D040081:Protein Array Analysis; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin; D000095002:Delta Catenin
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human