A switch from E-cadherin to N-cadherin expression indicates epithelial to mesenchymal transition and is of strong and independent importance for the progress of prostate cancer.
OBJECTIVE
Cell adhesion molecules are of crucial importance in cancer invasion and metastasis. Epithelial to mesenchymal transition, characterized by reduced E-cadherin and increased N-cadherin expression, has been recognized as a feature of aggressive tumors, but the importance of this phenotype has not been settled in human prostate cancer. We here present novel data, with special focus on the independent relationship between an E-cadherin to N-cadherin switch (EN-switch) and patient prognosis.


METHODS
Tissue microarray sections from a consecutive series of 104 radical prostatectomies during 1988 to 1994 with detailed clinicopathologic data and long follow-up were studied immunohistochemically for the expression of E-cadherin, N-cadherin, P-cadherin, beta-catenin, and p120(CTN).


RESULTS
Low E-cadherin expression was significantly associated with adverse clinicopathologic features, whereas other biomarkers were mostly related to Gleason score. In univariate survival analyses, cadherin switching (high N-cadherin and low E-cadherin) showed strong and significant associations with multiple end points of progression and cancer-specific death. Expression of the "basal cell marker" P-cadherin was associated with shorter time to skeletal metastasis (P = 0.036). In multivariate analysis of time to clinical recurrence, the "EN-switch" (hazard ratio, 4.3; P < 0.0005) had strong and independent prognostic effect, together with Gleason score.


CONCLUSIONS
These novel data unravel the importance of epithelial to mesenchymal transition for prostate cancer progression, and demonstration of a switch from E-cadherin to N-cadherin expression could have significant effect on the care of prostate cancer patients.
Gravdal
Karsten
K
The Gade Institute, Section for Pathology, University of Bergen, Haukeland University Hospital, Bergen, Norway.
Halvorsen
Ole J
OJ
Haukaas
Svein A
SA
Akslen
Lars A
LA
D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015820:Cadherins / Q000096:biosynthesis*; D051177:Catenins; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008648:Mesoderm / Q000473:pathology; D046228:Microarray Analysis; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000096:biosynthesis; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051176:beta Catenin / Q000096:biosynthesis; D000095002:Delta Catenin
D014408:Biomarkers, Tumor; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D051176:beta Catenin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human