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. 2023 Apr;30(4):462-472.
doi: 10.1002/jhbp.1253. Epub 2022 Nov 1.

Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation

Shoko Yamashita  1   2 , Chie Takasu  1 , Yuji Morine  1 , Hiroki Ishibashi  1 , Tetsuya Ikemoto  1 , Hiroki Mori  1 , Shinichiro Yamada  1 , Takeshi Oya  3 , Koichi Tsuneyama  2 , Mitsuo Shimada  1
Affiliations

Characteristic submucosal alteration in biliary carcinogenesis of pancreaticobiliary maljunction with a focus on inflammasome activation

Shoko Yamashita et al. J Hepatobiliary Pancreat Sci. 2023 Apr.

Abstract

Background: This study investigated submucosal alterations in biliary carcinogenesis of pancreaticobiliary maljunction (PBM).

Methods: Thirty-three patients with PBM (including seven with gallbladder [GB] cancer), four with neither biliary tract cancer nor PBM who underwent pancreaticoduodenectomy (controls), and seven with chronic cholecystitis without PBM were enrolled. Protein expression of α-smooth muscle actin (αSMA), CD68, and CD204 in the GB lamina propria and that of NLRP3 and caspase 1 in the GB epithelium and lamina propria were examined.

Results: Compared with the control and cholecystitis groups, αSMA expression was higher in the cancerous part (stroma) of the GB in patients with GB cancer + PBM and in the lamina propria of patients with PBM. The CD204/CD68 ratio in the lamina propria was higher in the PBM group than in the control and cholecystitis groups. NLRP3 and caspase 1 expression in both the lamina propria and epithelium was higher in the PBM than control group. In the PBM group, NLRP3- and caspase 1-positive cells in the lamina propria were located near the epithelium.

Conclusion: Activated fibroblasts and M2 macrophages in the GB lamina propria may be associated with biliary carcinogenesis of PBM, possibly through inflammasome activation.

Keywords: M2 macrophage; NLRP3; activated fibroblast; biliary cancer; caspase 1.

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