title: Histopathological characteristics of hypervascular cholangiocellular carcinoma as an early stage of cholangiocellular carcinoma.
abstract: OBJECTIVE
  Prognosis of hypervascular cholangiocellular carcinoma (h-CCC) is reportedly better than that of ordinary hypovascular CCC (o-CCC). The aim of this study is to clarify the histopathological characteristics of h-CCC.
  
  
  METHODS
  On the basis of the findings in the arterial phase of contrast-enhanced computed tomography, 16 cases of mass-forming-type CCC were divided into two groups (h-CCC, n = 8; o-CCC, n = 8). Areas of high (Area H-a) and low (Area H-b) attenuation in h-CCC cases and areas of low attenuation in o-CCC cases (Area O) were delineated. These areas were then evaluated histopathologically to determine the proportion of tumor cells, fibrous stroma, arterial vessel density, and immunohistochemical expression of Vascular endothelial growth factor; angiopoietin-2; cytokeratin 7, CK19, SOX9 and SOX17 genes; epithelial cell adhesion molecule; and the Bmi-1, Ki-67, epithelial membrane antigen and polyclonal carcinoembryonic antigen.
  
  
  RESULTS
  The areal ratio of tumor cells decreased and that of fibrous stroma increased in the following order: Area H-a, Area H-b and Area O. Values for AVD and neural cell adhesion molecule positivity rate were significantly higher in Area H-a than in Areas H-b or O. Expressions of vascular endothelial growth factor and angiopoietin-2 were significantly higher in Areas H-a and H-b than in Area O. The Ki-67 labeling index increased in the following order: Area H-a, Area H-b and Area O.
  
  
  CONCLUSIONS
  A high areal ratio of tumor cells and AVD as well as a high expression of stem cells and angiogenic markers were observed in cases of h-CCC, whereas the areal ratio of fibrous stroma and malignant potential were low. These results suggest that h-CCC may represent the early stage of CCC.
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan; Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Sato
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ojima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Onaya
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nara
authors.forename: Minoru
authors.initials: M
authors.lastname: Esaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Kenich
authors.initials: K
authors.lastname: Sugihara
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
keywords: angiogenesis; arterial vessel density; cholangiocellular carcinoma; dynamic computed tomography; immunohistochemistry; stem cell marker