Relation between aberrant alpha-catenin expression and loss of E-cadherin function in prostate cancer.
It is now well documented that E-cadherin expression correlates inversely with tumor grade in various carcinomas including prostate cancer. We also demonstrated a statistically significant correlation between decreased E-cadherin expression and progression-free period in early stage patients treated by radical prostatectomy and decreased survival in patients with advanced stage disease. We now study the relationship between E cadherin and alpha-catenin expression, because in prostate cancer cell lines, mutational inactivation of the alpha-catenin gene can be the cause of the impaired E-cadherin function. Twenty patients treated by radical prostatectomy and 32 advanced stage patients were evaluated immunohistochemically for E-cadherin and alpha-catenin expression. The results were related to tumor grade and disease progression. Four patients in the radical prostatectomy group had aberrant E-cadherin and alpha-catenin expression and showed disease progression. The other 16 patients were free of progression and had normal E-cadherin and alpha-catenin expression. In the advanced stage group, 4 of 13 patients with normal E-cadherin staining showed aberrant alpha-catenin expression and 2 patients (50%) progressed, compared with only 22% progression in patients with both normal E-cadherin and alpha-catenin expression. The other 19 patients with aberrant E-cadherin and alpha-catenin staining had the poorest prognosis. Our results suggest that loss of alpha-catenin expression could be one of the mechanisms responsible for the loss of E-cadherin-mediated cell-cell adhesion in human prostate cancer and might in some cases provide prognostic information.
Umbas
R
R
Department of Urology, University Hospital Nijmegen, The Netherlands.
Isaacs
W B
WB
Bringuier
P P
PP
Xue
Y
Y
Debruyne
F M
FM
Schalken
J A
JA
D014408:Biomarkers, Tumor; D015820:Cadherins / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000096:biosynthesis; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate; D013997:Time Factors; D051178:alpha Catenin
D014408:Biomarkers, Tumor; C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051178:alpha Catenin