Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer.
BACKGROUND
E-cadherin is an adhesion molecule involved in tumour invasion/metastasis. Silencing of E-cadherin by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. Helicobacter pylori is a class I carcinogen in gastric cancer.


OBJECTIVE
This study was undertaken to investigate the association between methylation of E-cadherin and H pylori in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer.


METHODS
E-cadherin methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. E-cadherin expression was studied by immunohistochemistry.


RESULTS
E-cadherin methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with H pylori infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. E-cadherin methylation was present in 0% (0/8) of normal mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. E-cadherin methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. E-cadherin methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05).


CONCLUSIONS
E-cadherin methylation is an early event in gastric carcinogenesis, and is initiated by H pylori infection.
Chan
A O-O
AO
Department of Medicine, Queen Mary Hospital, Hong Kong.
Lam
S-K
SK
Wong
B C-Y
BC
Wong
W-M
WM
Yuen
M-F
MF
Yeung
Y-H
YH
Hui
W-M
WM
Rashid
A
A
Kwong
Y-L
YL
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004415:Dyspepsia / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology
D015820:Cadherins; D009363:Neoplasm Proteins