P-cadherin expression in gastric carcinoma: its regulation mechanism and prognostic significance☆

Summary 

P-cadherin is a member of the cadherin family and is expressed in several solid tumors. This molecule was recently highlighted with the development of a new targeted compound being studied in a clinical trial on solid tumors. In the present study, we examined the protein and messenger RNA (mRNA) expression status of P-cadherin and its promoter methylation in gastric carcinoma cell lines and tissues. Of the 10 cell lines, 4 were found to express P-cadherin protein and mRNA, and the P-cadherin gene was found to be hypomethylated in its promoter region in these cell lines. Nonneoplastic gastric mucosal tissues from gastric carcinoma patients were negative for P-cadherin protein evaluated by immunohistochemistry and Western blotting and had a methylated P-cadherin promoter region. In carcinoma tissues, 70.8% (749/1058) of cases showed P-cadherin protein expression, and P-cadherin positive cases had a well or moderately differentiated histology according to the World Health Organization classification, intestinal-type histology by Lauren classification, and an earlier pT class. Furthermore, patients with P-cadherin expressing tumors had a favorable prognosis by univariate and multivariate survival analyses. In addition, P-cadherin protein expression was found to be significantly correlated with promoter hypomethylation. In summary, P-cadherin is silenced in nonneoplastic gastric mucosa, and P-cadherin expressing tumors constitute a subset of gastric carcinoma with intestinal-type histology and a favorable prognosis. In addition, our findings suggest that P-cadherin promoter methylation underlies the regulation of its expression. These findings may aid patient selection and the interpretation of P-cadherin targeted therapy and clinical trial results.

Keywords: P-cadherin, Stomach neoplasm, Methylation, Immunohistochemistry, Survival analysis