title: Elevated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in primary sclerosing cholangitis: ιmplications for cholangiocarcinogenesis.
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.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Minami, Hiroshima 734-8551, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Ishii
authors.forename: Tamito
authors.initials: T
authors.lastname: Sasaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Serikawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Minami
authors.forename: Akihito
authors.initials: A
authors.lastname: Okazaki
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yukutake
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishigaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kosaka
authors.forename: Teruo
authors.initials: T
authors.lastname: Mouri
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshimi
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimizu
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D001650:Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D063646:Carcinogenesis; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D015209:Cholangitis, Sclerosing / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone