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.

AID, p53 and MLH1 expression in early gastric neoplasms and the correlation with the background mucosa

“…Aberrant AID expression correlates with chronic active inflammation, glandular atrophy and IM in non-neoplastic gastric mucosa (26). The present study demonstrated that aberrant AID expression in tumors correlated with mononuclear cell activity in the mucosa surrounding the tumor, particularly in SMC cases, which supports the aforementioned mechanism of AID expression and is consistent with previous studies (26,27). Nagata et al (35) demonstrated that the enhanced expression of AID in human gastric mucosa infected by HP is reduced following HP eradication.…”

“…However, our previous study did not demonstrate an association between aberrant AID expression and p53 overexpression in early differentiated gastric cancer (26). Similarly, Goto et al (27) observed no correlation between AID and p53 expression in early differentiated and poorly-differentiated gastric cancer. In the present study, aberrant AID expression was significantly associated with p53 overexpression in the SMCs (P<0.01), but not in the MCs or adenomas.…”

Expression of activation-induced cytidine deaminase in oral epithelial dysplasia and oral squamous cell carcinoma

“…In addition, AID is expressed in epithelial cells of inflammatory lesions (10)(11)(12)(13)(14)(15). However, in the present SIN 1 and 2 tissues, immunohistochemical analysis revealed that AID tended to be expressed in oral TNF-α and siRNA had no effect on E-cadherin expression (A).…”

“…This mismatch induces somatic hypermutation and class-switch recombination in immunoglobulin genes, thereby producing high-affinity antibodies against specific antigens (7)(8)(9). It has also been reported that AID is expressed in cancer cells based on inflammatory conditions (3,(10)(11)(12)(13)(14)(15), and that it induces p53 mutation in gastric epithelial cells (16). These findings suggest that AID is associated with development of precancerous lesions and progression of malignant tumors.…”

Activation-induced cytidine deaminase mRNA expression in oral squamous cell carcinoma-derived cell lines is upregulated by inflammatory cytokines

“…Although AID is normally expressed in activated B cells, its expression has also been demonstrated in some inflammatory tissues, such as Helicobacter pylori-infected gastric epithelium and human colonic epithelium, and in some malignancies such as nonHodgkin lymphoma, hepatocellular carcinoma, lung cancer, and gastric cancer (7,(9)(10)(11)(12)(13)(14)(15). In addition, AID expression is upregulated by NF-κB via stimulation with inflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4 and IL-13 (7,(14)(15)(16), suggesting that AID acts as a linking factor between inflammation and cancer.…”