title: Hypervascular hepatocellular carcinomas showing hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging: a possible subtype with mature hepatocyte nature.
abstract: OBJECTIVE
  We evaluated molecular features of hypervascular hepatocellular carcinoma (HCC) that shows iso- or hyperintensity (hyperintense HCC) in the hepatobiliary phase (HB phase) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI).
  
  
  METHODS
  We investigated 89 surgically resected cases. Patients were divided into two groups according to the signal intensity in the HB phase of EOB-MRI: hyperintense HCCs (n = 18) and hypointense HCCs (n = 71). We performed immunohistochemical staining for uptake transporter of gadoxetic acid: organic anion transporter polypeptides (OATP8); tumor markers: alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II); hepatic stem cell markers: epithelial cell adhesion molecule (EpCAM), cytokeratin 19 (CK19), and neural cell adhesion molecule (NCAM); biliary marker: CK7; hepatocyte marker: hepatocyte paraffin 1 (HepPar1); markers of HCC differentiation: glypican-3; signaling: beta-catenin, and the respective grade was semiquantitatively determined.
  
  
  RESULTS
  Histopathologically, hyperintense HCCs showed significantly weaker expression of AFP (p < 0.05), PIVKA-II (p < 0.01), EpCAM (p < 0.005), glypican-3 (p < 0.005) relative to the hypointense HCCs, whereas OATP8 (p < 0.0001), HepPar1 (p < 0.05), and beta-catenin (p < 0.001) were overexpressed in hyperintense HCCs compared with hypointense HCCs.
  
  
  CONCLUSIONS
  Hyperintense HCC expressed OATP8 and showed a feature of mature hepatocytes with a weak expression of stem cell characteristics immunohistochemically. In addition, this type of HCC demonstrated a weaker expression of the poorer prognosis markers including, AFP, PIVKA-II, EpCAM, CK19, and glypican-3.
authors.affiliation: Department of Radiology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, 920-8640, Japan. noritin@f7.dion.ne.jp
authors.forename: Norihide
authors.initials: N
authors.lastname: Yoneda
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.forename: Azusa
authors.initials: A
authors.lastname: Kitao
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kita
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kozaka
authors.forename: Wataru
authors.initials: W
authors.lastname: Koda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gabata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000601:surgery; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000473:pathology* / Q000601:surgery; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; C073590:gadolinium ethoxybenzyl DTPA; D019786:Gadolinium DTPA