RUNX3 Methylation, Loss of RUNX3 Expression and Clinicopathologic Findings according to Helicobacter pylori CagA in Gastric Carcinoma.
OBJECTIVE
Helicobacter pylori cytotoxin-associated gene A (CagA) has been suggested to be involved in the inactivation of Runt-related transcription factor 3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear how H. pylori CagA initiates or maintains RUNX3 promoter methylation and inactivates its protein expression in gastric carcinoma.


METHODS
RUNX3 promoter methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76 sample pairs of gastric carcinoma tissue. The patients' medical records were reviewed. The association between RUNX3 methylation or loss of RUNX3 expression and clinicopathologic variables according to H. pylori CagA status were investigated.


RESULTS
In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation did not show association with lymphatic invasion, venous invasion, and TNM stages. However RUNX3 methylation was observed more frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H. pylori CagA-positive infection, loss of RUNX3 expression did not show association with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3 expression was observed more frequently in early gastric carcinoma than in advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not significant.


CONCLUSIONS
In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation or loss of RUNX3 expression did not show correlation with lymphovascular invasion and TNM stages. In early gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was observed more in poorly differentiated adenocarcinoma and signet ring cell carcinoma.
Departments of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.|Center for Health Promotion, Samsung Medical Center, Seoul, Korea.
Yoon Ju
YJ
Na
Departments of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Ki-Nam
KN
Shim
Departments of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Yang Hee
YH
Joo
Departments of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Seong-Eun
SE
Kim
Departments of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Hye-Kyung
HK
Jung
Departments of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
Sung-Ae
SA
Jung
Departments of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
Min Sun
MS
Cho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000150:complications / Q000382:microbiology / Q000473:pathology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; C080866:cagA protein, Helicobacter pylori
CagA; Carcinoma; Helicobacter pylori; Methylation; RUNX3