[Promoter methylation of several tumor suppressor genes in human gastric adenocarcinoma].
OBJECTIVE
To study the promoter methylation of several tumor suppressor genes in human gastric foveolar epithelia (GFE) of chronic gastritis, adjacent GFE of gastric adenocarcinoma (GAC) and GAC.


METHODS
Methylation specific PCR (MSP) technique was used to examine the promoter methylation of 4 tumor suppressor genes (E-cadherin, hMLH1, APC, and MGMT) in 106 paraffin-embedded specimens of GAC, including tumor tissues and adjacent GFE, and 16 paraffin-embedded specimens of GFE of chronic gastritis. Immunohistochemistry was used to detect the protein expression of E-cadherin (E-CD) in 46 out of the 106 cases of GAC.


RESULTS
The promoter methylation rates of tumor suppressor genes in the GAC tissue were 72.6% (77/106), significantly higher than that in the adjacent GFE (44.3%, 47/106) and the GFE of chronic gastritis (12.5%, 2/16, P < 0.01). The promote methylation rate of tumor suppressor genes in the GAC Laurén diffuse type was 80.6% (50/62), significantly higher than that of the GAC of intestinal type (61.4%, 27/44, P < 0.01). The rates of promoter methylation was significantly associated with depth of penetration, pTNM staging and degree of differentiation in GAC (all P < 0.05), but was no significantly associated with age, gender, Ming's classification and local lymph node metastasis (all P > 0.05). The rate of loss of E-CD protein expression or heterogeneously reduction of E-CD protein expression in the specimens of GAC with promoter methylation was 90.9% (20/22), significantly higher than that in the specimens of GAC without promoter methylation (9/24, 37.5%, P < 0.01).


CONCLUSIONS
Promoter methylation of above tumor suppressor genes is seldom found in the GFE of chronic gastritis, frequently found in the adjacent GFE of GAC, but very commonly in GAC. Promoter methylation may be an early event in the carcinogenesis of GAC. E-CD gene promoter methylation is closely related to loss or heterogeneously reduction of E-CD protein expression.
Cai
Jian-chun
JC
Department of Tumor Surgery, Xiamen Cancer Center, Xiamen First Hospital Affiliated to Fujian Medical University, Xiamen 361003, China.
Liu
Di
D
Zhang
Hai-ping
HP
Zhong
Shan
S
Xia
Ning-shao
NS
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes