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Aberrant activation-induced cytidine deaminase expression is associated with mucosal intestinalization in the early stage of gastric cancer

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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.

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Acknowledgments

The authors thank Ms. Y. Kamitani for her technical assistance. The English used in the manuscript was revised by Miss K. Miller (Royal English Language Centre, Fukuoka, Japan).

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Ayako Goto, Minako Hirahashi, Mikako Osada, Masazumi Tsuneyoshi & Yoshinao Oda

  2. Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Ayako Goto, Mikako Osada, Kazuhiko Nakamura & Ryoichi Takayanagi

  3. Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan

    Takashi Yao

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  1. Ayako Goto
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  4. Kazuhiko Nakamura
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Correspondence to Minako Hirahashi.

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Goto, A., Hirahashi, M., Osada, M. et al. Aberrant activation-induced cytidine deaminase expression is associated with mucosal intestinalization in the early stage of gastric cancer. Virchows Arch 458, 717–724 (2011). https://doi.org/10.1007/s00428-011-1086-x

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  • DOI: https://doi.org/10.1007/s00428-011-1086-x

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