Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis

Ishii,Yasutaka; Sasaki,Tamito; Serikawa,Masahiro; Minami,Tomoyuki; Okazaki,Akihito; Yukutake,Masanobu; Ishigaki,Takashi; Kosaka,Keiichi; Mouri,Teruo; Yoshimi,Satoshi; Shimizu,Akinori; Tsuboi,Tomofumi; Chayama,Kazuaki

doi:10.3892/ijo.2013.2038

Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Ιmplications for cholangiocarcinogenesis

Authors:
- Yasutaka Ishii
- Tamito Sasaki
- Masahiro Serikawa
- Tomoyuki Minami
- Akihito Okazaki
- Masanobu Yukutake
- Takashi Ishigaki
- Keiichi Kosaka
- Teruo Mouri
- Satoshi Yoshimi
- Akinori Shimizu
- Tomofumi Tsuboi
- Kazuaki Chayama
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Affiliations: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Minami, Hiroshima 734-8551, Japan
Published online on: July 24, 2013 https://doi.org/10.3892/ijo.2013.2038
Pages: 1073-1079

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Abstract

Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.

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