Aberrant E-cadherin and alpha-catenin expression in prostate cancer: correlation with patient survival.
E-cadherin maintains the normal differentiated phenotype in epithelial cells; this function is partly mediated by alpha-catenin, which links E-cadherin to the cell cytoskeleton. Dysfunction of E-cadherin in vitro and in vivo is associated with an invasive phenotype. However, the role of alpha-catenin is largely undetermined. We analyzed the expression of E-cadherin and alpha-catenin in prostate cancer to assess the relationship of abnormal expression to stage, grade and survival. E-cadherin expression was evaluated in 99 prostate cancers. In 79 of those specimens, alpha-catenin was also assessed. In benign prostatic epithelium, both E-cadherin and alpha-catenin were expressed uniformly at the cell membrane. Abnormal E-cadherin expression was found in 56% of cancer specimens, whereas alpha-catenin expression was abnormal in 42%. Abnormal expression of each molecule was significantly correlated with Gleason score (P < 0.0001) and the ratio of resection chippings infiltrated by tumor (P < 0.0001). E-cadherin expression was also associated with the extent of disease on the initial bone scan (P = 0.017). Univariate analysis showed significantly lower survival rate for patients with abnormal E-cadherin (P = 0.0003) or alpha-catenin expression (P = 0.031). Multivariate regression analysis showed that the prognostic value of E-cadherin was independent of tumor grade but not of metastasis. These results suggest that perturbation of cell-cell adhesion is involved in the progression of prostate cancer and that analysis of E-cadherin expression may be clinically useful.
Richmond
P J
PJ
Department of Surgery, Royal Free Hospital, London, United Kingdom.
Karayiannakis
A J
AJ
Nagafuchi
A
A
Kaisary
A V
AV
Pignatelli
M
M
D000368:Aged; D015820:Cadherins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051178:alpha Catenin