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Decreased E-Cadherin Immunoreactivity Correlates with Poor Survival in Patients with Bladder Tumors¹

Department of Urology, University Hospital, Nijmegen, the Netherlands [P. P. B., R. U., F. M. J. D., J. A. S.], and the Departments of Pathology [H. E. S.] and Urology [H. F. M. K.], Canisus Wilhelmina Hospital, Nijmegen, the Netherlands

E-cadherin, an intercellular adhesion molecule, has been shown to behave like an invasion suppressor gene in vitro. This may explain the inverse relation between expression of E-cadherin and tumor grade that was found in certain cancers. We therefore examined E-cadherin expression in bladder cancer samples from patients with known clinical follow-up. Forty-nine snap-frozen specimens (24 superficial and 25 invasive tumors) and 4 samples of normal urothelium were retrospectively analyzed with anti-E-cadherin monoclonal antibodies. In normal urothelium E-cadherin is expressed homogeneously with a typical membranous staining at cell-cell borders. Decreased expression is found in 5 of 24 superficial tumors and in 19 of 25 invasive cancers. Completely negative tumors are infrequent (4 cases). Most of the time a heterogeneous staining, which may correspond to an unstable E-cadherin expression during tumor development, is seen. Decreased E-cadherin expression correlates with both increased grade and stage (² = 9.5, P < 0.01, and ² = 14.9, P < 0.005, respectively). More importantly, abnormal E-cadherin expression correlates with shorter survival (log rank test: ² = 16.5, P < 0.001). In keeping with its in vitro invasion suppressor function, decreased E-cadherin expression correlates with the clinical aggressiveness of bladder tumors. This is the first report of E-cadherin as a marker with prognostic value. This parameter must now be tested in a large prospective study to assess its precise clinical relevance.

¹ P. P. B. was supported in part by the ARC (Association pour le Recherche sur le Cancer, Villejuif, France) and FUSEX (Foundation for Urological Scientific Exchange, Nijmegen, the Netherlands), and R. U. was supported by the Netherlands Universities Foundation for International Cooperation and van Deventer-Maasstichting. This work was supported by Dutch Cancer Foundation Grants NUKC 9001 and 9102.

² To whom requests for reprints should be addressed, at the Urological Research Laboratory, University Hospital Nijmegen, P. O. Box 9101, 6500HB Nijmegen, the Netherlands.

Received 3/26/93. Accepted 6/ 2/93.

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