Expression of classic cadherins type I in urothelial neoplastic progression

Loss or reduced expression of E-cadherin has been shown to be associated wi th poor survival in patients with bladder cancer. In numerous cases, loss o f E-cadherin expression in bladder tumors has been accompanied by continued association of catenins with the membrane, suggestive of the expression of an alternative cadherin member. In this study we examined 75 bladder tumor s using immunohistochemistry for the expression of E-, P-cadherin, and alph a-, beta-, and gamma -catenins. As reported previously, loss or reduced E-c adherin expression is a frequent event in late stage bladder cancer, accomp anied by less frequent alterations associated with different catenin family members. Analysis of 51 tumors for expression of E-, P-, and N-cadherin sh owed P-cadherin localized to the basal cell layers of normal urothelium, wi th retention of expression in the majority of tumors. In low-grade tumors P -cadherin was found localized to an expanded basal cell compartment, contra sting with the more extensive staining observed in late stage tumors. Membr anous P-cadherin staining was often found in the absence of E-cadherin stai ning. N-cadherin is not expressed in normal bladder mucosa, but detection o f this cadherin member was recorded in 39% (20/51) of bladder tumors. Unlik e P-cadherin, membranous N-cadherin was detected in focal regions within tu mors, representing novel expression in urothelial neoplastic progression. A lthough focal N-cadherin staining was observed in 3 noninvasive lesions, th e majority of tumors expressing N-cadherin were invasive (17/20). Coexpress ion of E-, P-, and N-cadherin was recorded in 5 grade 2 bladder tumors. Exp ression of P-cadherin is maintained throughout bladder tumorigenesis, accom panied by aberrant expression of N-cadherin. Clearly, neither P- nor N-cadh erin act in an invasive-suppressor mode in bladder cancer, but whether they have a primary role to play in urothelial neoplastic progression has yet t o be established. Copyright (C) 2001 by W.B. Saunders Company