title: Preserved or enhanced OATP1B3 expression in hepatocellular adenoma subtypes with nuclear accumulation of β-catenin.
abstract: OBJECTIVE
  Recent studies have indicated that hepatocellular adenoma (HCA) is a heterogenous group of benign tumors with various genetic and clinicopathological characteristics. We delineated the clinicopathological characteristics of HCA subtypes and evaluated the expression of transporter protein OATP1B3 in HCA.
  
  
  METHODS
  HCA in 34 Japanese patients were investigated immunohistochemically and classified into four subtypes (HNF1α-inactivated type, H-HCA; β-catenin-activated type, b-HCA; inflammatory type, I-HCA; unclassified type, u-HCA). Immunostaining of OATP1B3 protein in HCA tissue sections was performed to determine the association between OATP1B3 expression and HCA subtypes.
  
  
  RESULTS
  HCA was categorized into the following four subtypes and two combined subtypes: 10 H-HCA (29%), 10 I-HCA (29%), seven b-HCA (21%), two b-HCA/H-HCA (6%), two b-HCA/I-HCA (6%) and three u-HCA (9%). The male-to-female ratio was 18:16. Oral contraceptive use was rare but seven HCA were found in patients with glycogen storage disease, congenital absence of the portal vein and idiopathic portal hypertension. OATP1B3 expression was decreased in 24 HCA but was preserved or increased in 10 HCA. All nine HCA with nuclear staining for β-catenin showed preserved or enhanced OATP1B3 expression, indicating a significant association between nuclear β-catenin accumulation and OATP1B3 expression in HCA.
  
  
  CONCLUSIONS
  HCA subtype classification was validated in 91% of our Japanese subjects although their clinical backgrounds including rare contraceptive use were different from European subjects. A close association between preserved or enhanced OATP1B3 expression and b-HCA subtype indicated important modalities for clinical decisions in the treatment and follow up of patients with HCA.
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Soejima
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Fukuo
authors.initials: F
authors.lastname: Kondo
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.|Department of Diagnostic Pathology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aso
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Sano
authors.affiliation: Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Sanada
authors.affiliation: Department of Pathology, Jichi Medical University, Tochigi, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
keywords: OATP1B3; glutamine synthetase; hepatocellular adenoma; liver fatty acid-binding protein; serum amyloid A; β-catenin