Decreased expression of catenins (alpha and beta), p120 CTN, and E-cadherin cell adhesion proteins and E-cadherin gene promoter methylation in prostatic adenocarcinomas

BACKGROUND. Catenin/E-cadherin complex proteins play an important role in c ell-cell adhesion with decreased expression correlating with adverse progno stic variables in several human malignancies. METHODS. Archival formalin fixed, paraffin embedded (FFPE) sections from 11 8 prostatic adenocarcinomas (PACs) were immunostained by an automated metho d (Ventana Medical Systems, Tuscon, AZ) using monoclonal antibodies to cate nins alpha and beta, p120 CTN, and E-cadherin proteins. Immunoreactivity wa s semiquantitatively graded, and results correlated with traditional progno stic parameters. In alpha subset of 10 randomly selected cases, E-cadherin gene promoter methylation status was determined on FFPE tissues using sodiu m bisulfite/hydroquinone DNA modification and polymerase chain reaction (PC R) with methylation specific primers (CpG wiz E-cadherin methylation assay; Intergen Co., Purchase, NY). RESULTS. Decreased expression of alpha -catenin (17%), beta catenin (4%), p 120 CTN (45%), and E-cadherin (25%) proteins was noted in PACs with downreg ulation of each protein correlating with high tumor grade (P = 0.01-0.0001) . In addition, p120 CTN and E-cadherin expression levels correlated with pa thologic I stage (P 0.05; P = 0.02), aneuploidy (P = 0.001; P = 0.0001), an d alpha -catenin with aneuploidy (P = 0.0001). p120 CTN loss also correlate d with preoperative serum prostate specific antigen (P = 0.05). Two of 10 c ases featured no evidence of E-cadherin gene promoter methylation by PCR an d both cases retained expression of E-cadherin protein on immunohistochemis try. Of the 8 cases that showed E-cadherin methylation, 5 (68%) featured lo ss of expression of the protein on immunohistochemistry (P = 0.11). There w as no correlation between E-cadherin methylation and adverse prognostic var iables. CONCLUSIONS Decreased expression of catenin/E-cadherin complex cell adhesio n proteins is associated with aggressive phenotype in prostatic adenocarcin oma. E-cadherin gene promote methylation is a common event in prostate carc inoma but does not appear to bear prognostic significance in the subset of cases analyzed. Cancer 200 1;92:2786-95. (C) 2001 American Cancer Society.