Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p 120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas

Cell adhesion molecule expression has been linked to disease outcome in pro static adenocarcinomas (PACs). We evaluated the coordinated expression of c atenin-related proteins, E-cadherin, N-cadherin, and CD44s in PACs. Archiva l sections from 112 PACs were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using monoclonal antibodies to alpha- and bet a -catenins, p120CTN, E-cadherin, N-cadherin, and CD44s proteins. Immunorea ctivity was semiquantitatively scored, and results were evaluated for assoc iation between these markers. Staining results were also correlated with tu mor grade, stage, ploidy, preoperative serum PSA, and postoperative biochem ical disease recurrence. Decreased expression of alpha- and beta- catenins, p120CTN, E-cadherin, and CD44s proteins (range, 5% to 49%) was noted in PA Cs, and downregulation of each of these proteins correlated with high tumor grade (P = .02 to .0001). Although loss of E-cadherin and p120CTN each cor related with stage (E-cadherin, P = .02; p120CTN, P = .02) and ploidy (E-ca dherin, P = .0001; p120CTN, P = .004), downregulation of CD44s correlated w ith ploidy (P = .002), serum PSA (P = .005), and postoperative disease recu rrence (P = .02). N-cadherin was positive in only 5% of PACs and did not co rrelate with any prognostic parameters. alpha -Catenin downregulation corre lated with decreased expression of E-cadherin (P = .0001). Additionally, de creased expression of each of these 2 proteins respectively correlated with loss of beta -catenin (P = .0001 and .004), p120CTN (P = .005 and .001), a nd CD44s (P = .008 and .01). beta -Catenin expression levels correlated wit h p120CTN (P = .01). A trend for co-downregulation of CD44s and p120CTN and of CD44s and beta -catenin was observed. In conclusion, the significant as sociation between decreased expression of various members of the CAM family of proteins supports their collective role in mediating cell-cell adhesion . Altered expression of these proteins may be of prognostic value in patien ts with prostate cancer. Him PATROL 32: 849-855. (C) 2001 by W.B. Saunders Company.