Objective   To investigate the promoter methylation of Wif-1 in gastric cardiac adenocarcinoma (GCA).   Methods   Tumor samples of 94 cases of GCA before chemotherapy and radiotherapy admitted in our hospital from January 2004 to December 2006 were collected

and their normal mucosal tissues served as normal control. Nested methylation-specific PCR (MSP) and RT-PCR were applied respectively to examine the Wif-1 promot

er methylation and its mRNA expression in tumors and corresponding normal mucosal tissues. Immunohistochemical staining was used to determine the protein expression of β-catenin. The correlation of the Wif-1 methylation and clinical data was analyzed.   Results   The frequency of Wif-1 promoter methylation in GCA and corresponding normal mucosa were 61.7% (58/94) and 34.0% (32/94)

respectively. The frequency of Wif-1 promoter methylation in GCA was significantly higher than that in normal mucosa (χ

2

=14.409

P=0.000). In the tissues of GCA and normal mucosa

the positive rate of Wif-1 mRNA expression were 10.6% (10/94) and 86.2% (81/94)

and the protein expression of β-catenin were 90.4% (85/94) and 38.3% (36/94). The expression of Wif-1 mRNA and β-catenin protein were correlated with the frequency of Wif-1 methylation in the GCA tissues (P0.01). Furthermore

the frequency of Wif-1 methylation was correlated with the invasion depth and lymphatic metastasis (P0.05)

but not with pathological classification and clinical stage.    Conclusion   CpG methylation of the Wif-1 promoter is a frequent event in GCA and may contribute to pathogenesis of GCA through aberrant canonical Wnt/ β-catenin signaling pathway.