Disordered beta-catenin expression and E-cadherin/CDH1 promoter methylation in gastric carcinoma.
OBJECTIVE
To investigate the distribution of beta-catenin in nuclei or membrane/cytoplasm of gastric carcinoma cells, the relationship between E-cadherin gene methylation and its expression, and the role of beta-catenin and E-cadherin as potential molecular markers in predicting tumor infiltration.


METHODS
Twenty-nine cases of gastric carcinoma, classified as diffuse and intestinal variants, were selected for study. Nuclear and cytoplasmic proteins were purified and beta-catenin content was detected by ELISA. DNA methylation of E-cadherin/CDH1 gene promoter was studied by methylation-specific PCR and compaired with E-cadherin expression detected by immunohistochemistry.


RESULTS
In 27 cases of gastric carcinoma, the ratio of beta-catenin content between nuclei and membrane/cytoplasm was correlated with the T-classification (r = 0.392, P = 0.043). The significance was present between T2 and T3 groups. No correlation was detected between diffuse and intestinal variants in terms of their beta-catenin distribution. In 21 cases of diffuse variants of gastric carcinoma, there was a difference in E-cadherin expression between CDH1 gene-methylated group and non-methylated group (29 % vs 71 %, P = 0.027). No correlation between CDH1 gene methylation and T-classification was found, neither was the significance between E-cadherin expression and tumor infiltration grade.


CONCLUSIONS
Comparative analysis of nuclear and membrane/cytoplasmic beta-catenin can predict local tumor infiltration. E-cadherin/CDH1 gene methylation is an important cause for its gene silence in diffuse variant gastric carcinoma. Methylation of CDH1 gene in the absence of E-cadherin is an early event in gastric carcinogenesis.
Wang
Li
L
Department of Pathology, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
Zhang
Fan
F
Wu
Ping-Ping
PP
Jiang
Xu-Cheng
XC
Zheng
Lin
L
Yu
Ying-Yan
YY
D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D005819:Genetic Markers; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D004273:DNA, Neoplasm; D005819:Genetic Markers; D051176:beta Catenin