Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors.
Loss of E-cadherin-mediated adhesion is an important step in the progression of many carcinomas. In model systems, it has been shown that cadherin function requires not only proper E-cadherin expression but also its linkage to the cytoskeleton through catenins. Hence, defects in catenins may cause defective E-cadherin function, and catenins as well as E-cadherin might constitute prognostic indicators. Here, we extend our previous study on E-cadherin in bladder cancer (Cancer Res., 53: 3241-3245, 1993). We have evaluated the expression of E-cadherin-associated cytoplasmic molecules (alpha-, beta-, and gamma-catenins and p120cas) to clarify whether or not the pattern of their expression could provide additional prognostic information beyond that from E-cadherin alone. Forty-eight frozen bladder tumor specimens and 9 samples of normal urothelium were studied by immunohistochemistry. A discrepancy between the E-cadherin and catenin expression pattern was seen in 20.8% of cases. Abnormal expression of each molecule is significantly correlated with tumor grade (P < 0.01) and stage (P < 0.01). Reduced expression of all of the molecules correlates with poor survival (P < 0.01 for each variable). Proportional hazard regression analysis showed that beta-catenin, E-cadherin, and alpha-catenin have strong predictive value, whereas plakoglobin and p120cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, alpha-catenin, or beta-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, beta-catenin, E-cadherin, and alpha-catenin have similar prognostic values. Therefore, from a practical point of view, the expression of any of these proteins can be of prognostic value for patients with bladder cancer.
Shimazui
T
T
Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Schalken
J A
JA
Giroldi
L A
LA
Jansen
C F
CF
Akaza
H
H
Koiso
K
K
Debruyne
F M
FM
Bringuier
P P
PP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000096:biosynthesis; D003131:Combined Modality Therapy; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000096:biosynthesis; D051180:Desmoplakins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000032:analysis* / Q000096:biosynthesis; D011379:Prognosis; D015996:Survival Rate; D013997:Time Factors; D015534:Trans-Activators; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin
D014408:Biomarkers, Tumor; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D010750:Phosphoproteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin; C000722347:CTNND1 protein, human