Detection of promoter hypermethylation of the CpG island of E-cadherin in gastric cardiac adenocarcinoma.
OBJECTIVE
Abnormal hypermethylation of CpG islands associated with tumor suppressor genes can lead to transcriptional silencing in neoplasia. The aim of this study was to investigate the promoter methylation and expression of E-cadherin gene in gastric cardiac adenocarcinoma (GCA).


METHODS
A nested MSP approach, immunohistochemistry method and RT-PCR were used respectively to examine the methylation status of the 5' CpG island of E-cadherin, its protein expression and mRNA expression in tumors and corresponding normal tissues.


RESULTS
E-cadherin was methylated in 63 of 92 (68.5%) tumor specimens, which was significantly higher than that in corresponding normal tissues (P<0.001). Methylation frequencies of stage III and IV tumor tissues was significantly higher than that in stage I and II tumor tissues (P = 0.01). Methylation status of poor differentiation group was significantly higher than moderate and poor-moderate differentiation groups (P<0.01). By immunostaining 51 of 92 tumor tissues demonstrated heterogeneous, positive immunostaining of tumor tissues (44.6%), significantly different from matched normal tissues (P<0.001). Positive immunostaining of stage III and IV tumor tissues was significantly lower than stage I and II tumor tissues (P<0.01). Poor differentiation group was also significantly lower than moderate and poor-moderate differentiation groups (P<0.05). 80 percent of tumor tissues with E-cadherin gene methylated showed inactivated mRNA expression.


CONCLUSIONS
High methylation status of the 5' CpG island of E-cadherin gene may be one of the mechanisms in the development of gastric cardiac adenocarcinoma.
Guo
W
W
Department of Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Dong
Zhiming
Z
Guo
Y
Y
Kuang
G
G
Yang
Z
Z
Chen
Z
Z
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D002299:Cardia; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D015820:Cadherins; D012333:RNA, Messenger