title: Angiogenesis in cholangiocellular carcinoma: expression of vascular endothelial growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological significance.
abstract: Angiogenesis in cholangiocellular carcinoma (CCC) has rarely been investigated. The aim of this study was to determine the angiogenesis status of CCC and assess its relationship with angiogenic factors and clinicopathological characteristics. We examined 33 surgically resected CCC specimens. Tumor angiogenesis was assessed by microvessel density (MVD) using the anti-CD34 antibody, and the expression of VEGF, Ang-1, Ang-2, and TSP-1 was determined by immunohistochemistry. The mean (+/- SD) MVD was 87.2+/-52.6/mm2 (range, 0-229/mm2). A total of 75.6% cases were positive for VEGF expression, 36% for Ang-1, 57.6% for Ang-2 and 45.5% for TSP-1. VEGF and Ang-2 expression was associated with a significantly higher level of MVD (p=0.004 and 0.015, respectively). TSP-1 expression was associated with a significantly lower level of MVD (p=0.005) and a higher level of intrahepatic metastasis (46.7% vs. 5.6%, p=0.012). There was no significant correlation between VEGF, Ang-1, Ang-2, and TSP-1 expression and tumor size, capsule formation, infiltration of capsule, portal vein invasion, intrahepatic metastasis or CCC differentiation. There was no significant correlation between MVD levels, VEGF, Ang-1, Ang-2, and TSP-1 expression and postoperative survival. A considerable degree of angiogenesis, comparable to that of other solid tumors, was observed in CCC. VEGF and Ang-2 might play a proangiogenic role, and TSP-1 may play an inhibitory role in CCC. Although TSP-1 may increase intrahepatic CCC metastases, neither MVD levels nor the expression of VEGF, Ang-1, or Ang-2 was associated with clinicopathological factors and prognosis.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, Japan.
authors.forename: Di
authors.initials: D
authors.lastname: Tang
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Motoi
authors.initials: M
authors.lastname: Kondo
authors.forename: Hideo
authors.initials: H
authors.lastname: Ota
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kato
authors.forename: Bazarragchaa
authors.initials: B
authors.lastname: Damdinsuren
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Kenichi
authors.initials: K
authors.lastname: Wakasa
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000032:analysis; D042702:Angiopoietin-2 / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001650:Bile Duct Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000601:surgery; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000098:blood supply* / Q000378:metabolism / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D019700:Thrombospondin 1 / Q000032:analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018952:Antigens, CD34; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A