title: Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia.
abstract: Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes correlating with the presence of intestinal metaplasia that occur in the gastric mucosa prior to neoplastic transformation. The aim of this study was to compare the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori eradication between subjects at high risk for gastric cancer and controls. The usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis was also examined. Seventy patients with endoscopic resection for early gastric cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by immunostaining. Serum levels of pepsinogen I before eradication in the patients scored as having improvement of corpus atrophy were significantly higher than in the patients without improvement (<0.01). Residual inflammation at the corpus lesser curve was more frequently detected in the cancer group than in the controls (OR 4.6 95% C.I. 1.6-13.5) and in the mucosa with incomplete intestinal metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6 95% C.I. 2.4-24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser curve significantly improved in mucosa without incomplete intestinal metaplasia (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In conclusion, H. pylori eradication prior to development of incomplete intestinal metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I may be a useful marker in patients with a residual higher risk of gastric cancer after H. pylori eradication.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan. shiotani@med.kawasaki-m.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Shiotani
authors.forename: Noriya
authors.initials: N
authors.lastname: Uedo
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iishi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Tatsuta
authors.forename: Shingo
authors.initials: S
authors.lastname: Ishiguro
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Nakae
authors.forename: Tomoari
authors.initials: T
authors.lastname: Kamada
authors.forename: Ken
authors.initials: K
authors.lastname: Haruma
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D017291:Clarithromycin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005756:Gastritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D053823:Hedgehog Proteins / Q000096:biosynthesis* / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D011230:Precancerous Conditions / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C509239:SHH protein, human; D000658:Amoxicillin; D020116:Pepsinogen A; D017291:Clarithromycin