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

原発性硬化性胆管炎ではcyclooxygenase-2とmicrosomal prostaglandin E synathase-1の発現が亢進し、胆管発がんへの関与が示唆される

Ishii Yasutaka

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.

primary sclerosing cholangitis

cyclooxygenase-2

microsomal prostaglandin E synthase-1

cholangiocarcinoma

Medical sciences [ 490 ]

eng

Copyright(c) by Author

[Created] 2014-11-21

Yasutaka Ishii, Tamito Sasaki, Masahiro Serikawa, Tomoyuki Minami, Akihito Okazaki, Masanobu Yukutake, Takashi Ishigaki, Keiichi Kosaka, Teruo Mouri, Satoshi Yoshimi, Akinori Shimizu, Tomofumi Tsuboi and Kazuaki Chayama; Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: Implications for cholangiocarcinogenesis; INTERNATIONAL JOURNAL OF ONCOLOGY 43: 1073-1079, 2013 (DOI: 10.3892/ijo.2013.2038) references

[DOI] http://dx.doi.org/10.3892/ijo.2013.2038 references

広島大学