P-cadherin expression in gastric carcinoma: its regulation mechanism and prognostic significance.
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.
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Min A
MA
Kim
Eun Ji
EJ
Jung
Hye Seung
HS
Lee
Hee Eun
HE
Lee
Han-Kwang
HK
Yang
Do-Youn
DY
Oh
Yung-Jue
YJ
Bang
Woo Ho
WH
Kim
D000704:Analysis of Variance; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008745:Methylation; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology
D015820:Cadherins; D012333:RNA, Messenger