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Prognostic Value of Cadherin-associated Molecules (-, ß-, and -Catenins and p120^cas) in Bladder Tumors

Urological Research Laboratory, University Hospital Nijmegen, Nijmegen, the Netherlands [T. S., J. A. S., L. A. G., C. F. J. J., F. M. J. D., P. P. B.]; Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-city, Ibaraki, Japan [T. S., H. A., K. K.]; and Veterinary Faculty, University of Utrecht, Utrecht, the Netherlands [J. A. S.]

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 (-, ß-, and -catenins and p120^cas) 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 ß-catenin, E-cadherin, and -catenin have strong predictive value, whereas plakoglobin and p120^cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, -catenin, or ß-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, ß-catenin, E-cadherin, and -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.

¹ To whom requests for reprints should be addressed, at Urological Research Laboratory, University Hospital Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, the Netherlands. Phone: 31-24-3614974; Fax: 31-24-3541222.

² Present adress: Unit of Molecular Pathology, IARC, Lyon, France.

Received 4/ 1/96. Accepted 7/15/96.

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