Intracellular and interstitial expression of Helicobacter pylori virulence genes in gastric precancerous intestinal metaplasia and adenocarcinoma.
Gastric intestinal metaplasia (IM) and gastric cancer are associated with Helicobacter pylori, but the bacterium often is undetectable in these lesions. To unravel this apparent paradox, IM, H. pylori presence, and the expression of H. pylori virulence genes were quantified concurrently using histologic testing, in situ hybridization, and immunohistochemistry. H. pylori was detected inside metaplastic, dysplastic, and neoplastic epithelial cells, and cagA and babA2 expression was colocalized. Importantly, expression of cagA was significantly higher in patients with IM and adenocarcinoma than in control subjects. The preneoplastic "acidic" MUC2 mucin was detected only in the presence of H. pylori, and MUC2 expression was higher in patients with IM, dysplasia, and cancer. These novel findings are compatible with the hypothesis that all stages of gastric carcinogenesis are fostered by persistent intracellular expression of H. pylori virulence genes, especially cagA inside MUC2-producing precancerous gastric cells and pleomorphic cancer cells.
Semino-Mora
Cristina
C
Laboratory of Gastrointestinal and Liver Studies, Digestive Diseases Division, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Doi
Sonia Q
SQ
Marty
Aileen
A
Simko
Vlado
V
Carlstedt
Ingemar
I
Dubois
Andre
A
D000230:Adenocarcinoma / Q000382:microbiology* / Q000648:ultrastructure; D018829:Adhesins, Bacterial; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015169:Colony Count, Microbial; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000382:microbiology*; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000648:ultrastructure; D014774:Virulence / Q000235:genetics
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; C400429:BabA protein, Helicobacter pylori; D001426:Bacterial Proteins; D002352:Carrier Proteins; D012329:RNA, Bacterial; C080866:cagA protein, Helicobacter pylori