Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer.
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.
Stefansson
Ingunn M
IM
Department of Pathology, the Gade Institute, Haukeland University Hospital, Bergen, Norway.
Salvesen
Helga B
HB
Akslen
Lars A
LA
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
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