[CpG island methylation of E-cadherin gene promoter in gastric carcinoma].
OBJECTIVE
Transcriptional silencing by CpG island methylation is now believed to be an important mechanism of carcinogenesis. E-cadherin can suppress tumor cell invasion and metastasis, and is considered as an invasion/metastasis suppressor gene. Inactivation of E-cadherin gene often occurs in poorly differentiated gastric carcinoma. This study was to investigate the CpG island methylation status of E-cadherin gene promoter in primary human gastric carcinomas and adjacent gastric tissues, and to explore the mechanism of gastric carcinogenesis.


METHODS
The CpG island methylation status of E-cadherin gene promoter in 51 specimens of primary human gastric carcinoma, 37 specimens of adjacent gastric tissue, and 12 specimens of normal gastric mucosa was detected by methylation-specific polymerase chain reaction (MSP). The expression of E-cadherin was evaluated by immunohistochemistry.


RESULTS
The CpG island methylaion was not detected in normal gastric mucosa, but detected in 32 (62.7%) gastric carcinoma specimens and 4 (10.8%) adjacent gastric specimens. It occurred more frequently in poorly differentiated carcinomas than in well differentiated carcinomas [72.2% (26/36) vs. 33.3% (6/15), P<0.01], and it was presented at similar rates in stage T1/T2 carcinomas and stage T3/T4 carcinomas [55.6% (10/18) and 66.7% (22/33), P>0.05]. Down-regulation of E-cadherin expression was detected in 84.5% (27/32) tumor tissues with methylated CpG island and 26.3% (5/19) tumor tissues with unmethylated CpG island. No statistical correlation was found between CpG island methylaion and Helicobacter pylori infection.


CONCLUSIONS
The CpG island methylaion of E-cadherin gene promoter commonly exists in gastric carcinoma, particularly in poorly differentiated adenocarcinoma. E-cadherin promoter methylation may be involved in the early process of gastric carcinogenesis, but has no correlation to Helicobacter pylori infection.
Zhou
Yong-Ning
YN
Center of Endoscopy, The First Hospital, Lanzhou University, Lanzhou, Gansu, P. R. China. yongningzhou@sina.com.cn
Xu
Cai-Pu
CP
Han
Biao
B
Ji
Rui
R
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D015820:Cadherins