title: Aberrant activation-induced cytidine deaminase expression is associated with mucosal intestinalization in the early stage of gastric cancer.
abstract: Although Helicobacter pylori is a risk factor for gastric cancer (GC), its detailed carcinogenesis remains unclear. Recently, aberrant expression of activation-induced cytidine deaminase (AID) was demonstrated in gastric epithelium with H. pylori infection and seems to cause the accumulation of mutation. This investigation aims to elucidate whether or not AID expression plays an important role in the carcinogenesis of early GC. We examined the correlation between immunohistochemical AID expression and histological characteristics, including pre-existing chronic gastritis and cellular mucin phenotype in 138 cases of intramucosal GC. Furthermore, we investigated the relationship between AID, p53 protein, and β-catenin. The low degree of polymorphonuclear neutrophil activity, and the high degree of glandular atrophy and intestinal metaplasia were significantly correlated with the high levels of AID expression in non-neoplastic mucosa (P = 0.007, P ≤ 0.001, and P = 0.003). With regard to mucin phenotype of carcinoma, the intestinal phenotype tended to have the higher AID expression levels (P = 0.052). AID showed close correlations with Cdx2 and nuclear staining of β-catenin (P = 0.003, P = 0.034). As for p53 protein, no correlation was found with AID expression. Our findings suggest that aberrant AID expression is correlated with persistent inflammatory condition induced by H. pylori infection and may contribute to the development of GC through an inflammatory condition and intestinalization.
authors.affiliation: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Goto
authors.forename: Minako
authors.initials: M
authors.lastname: Hirahashi
authors.forename: Mikako
authors.initials: M
authors.lastname: Osada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071616:CDX2 Transcription Factor; D003564:Cytidine Deaminase / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D003564:Cytidine Deaminase