DECREASED E-CADHERIN IMMUNOREACTIVITY CORRELATES WITH POOR SURVIVAL IN PATIENTS WITH BLADDER-TUMORS

E-cadherin, an intercellular adhesion molecule, has been shown to beha ve like an invasion suppressor gene in vitro. This may explain the inv erse relation between expression of E-cadherin and tumor grade that wa s found in certain cancers. We therefore examined E-cadherin expressio n in bladder cancer samples from patients with known clinical follow-u p. Forty-nine snap-frozen specimens (24 superficial and 25 invasive tu mors) and 4 samples of normal urothelium were retrospectively analyzed with anti-E-cadherin monoclonal antibodies. In normal urothelium E-ca dherin is expressed homogeneously with a typical membranous staining a t cell-cell borders. Decreased expression is found in 5 of 24 superfic ial tumors and in 19 of 25 invasive cancers. Completely negative tumor s are infrequent (4 cases). Most of the time a heterogeneous staining, which may correspond to an unstable E-cadherin expression during tumo r development, is seen. Decreased E-cadherin expression correlates wit h both increased grade and stage (chi2 = 9.5, P < 0.01, and chi2 = 14. 9, P < 0.005, respectively). More importantly, abnormal E-cadherin exp ression correlates with shorter survival (log rank test: chi2 = 16.5, P < 0.001). In keeping with its in vitro invasion suppressor function, decreased E-cadherin expression correlates with the clinical aggressi veness 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 l arge prospective study to assess its precise clinical relevance.