271 Cathelicidin Inhibits Colitis Associated Colon Cancer Development by Inhibition of Epithelial-Mesenchymal Transition and Cancer Associated Fibroblasts

Oxyntic atrophy and intestinal metaplasia are considered critical precursors for the development of gastric adenocarcinoma. Autoimmune atrophic gastritis (AAG) is characterized by immune-mediated destruction of gastric parietal cells, chronic inflammation, atrophic gastritis, and pernicious anemia. While AAG is associated with increased risk of carcinoids, the risk for adenocarcinoma in the absence of H. pylori infection is controversial. Here, we investigated the differences between AAG and chronic atrophic gastritis (CAG) with intestinal metaplasia (IM). Methods: Tissue from 6 patients with CAG were obtained at the time of resection for gastric adenocarcinomna and all patients showed IM. 20 AAG patients were diagnosed by upper endoscopy, oxyntic atrophy, and the presence of anti-parietal cell antibodies. 20/20 AAG patients were negative for H. pylori. 19/20 AAG patient showed marked elevations in both serum gastrin and serum chromogranin. In the body mucosa, we evaluated the presence of spasmolytic-polypeptide expressing metaplasia (SPEM) with TFF2 staining, IM with MUC2, macrophages with CD68, neutrophils with myeloperoxidase (MPO) and proliferative cells with Ki67. Results: 20/20 AAG patients showed profound parietal cell loss with SPEM and 15 demonstrated IM (75%). AAG patients had significantly fewer MPO positive neutrophils (6.4/1000 cells) compared to CAG patients (21.9/1000 cells) (p<0.01). The gastric biopsies from AAG patients also showed significantly fewer CD68 positive macrophages (10.1/1000 cells) compared to CAG patients (17.4/1000 cells, p= 0.01). Ki67 positive cells were markedly decreased in AAG patients (0.2/1000 cells) compared to CAG patients (14.5/1000 cells) (p<0.01). Conclusions: The metaplasia observed in AAG patients exhibited a low proliferative rate compared with the metaplasia samples from CAG patients. This lower proliferative rate was associated with smaller macrophage and neutrophil numbers in AAG patients compared to those in CAG patients. The lower proliferative rate in metaplasia and reduced macrophage and neutrophil infiltrates may explain in part the lower tendency of metaplasia in H. pylori-negative AAG patients to evolve into gastric adenocarcinoma compared with individuals with CAG.