title: Expression of indocyanine green-related transporters in hepatocellular carcinoma.
abstract: BACKGROUND
  Indocyanine green (ICG), an organic anion used in liver function tests, is known to accumulate in hepatocellular carcinoma (HCC) tissues after an intravenous injection. Because the intratumoral expression of transporters for chemical agents influences the behaviors of some malignant tumors, we investigated whether the expression of ICG-related transporters influenced the clinicopathologic features of HCC.
  
  
  METHODS
  ICG accumulation patterns were examined using near-infrared spectroscopy and the protein expression of ICG-related transporters was assessed using immunohistochemistry and immunoblotting in 40 resected HCC specimens. We also determined whether the intratumor expression of these transporters affected intratumor lipid composition by imaging mass spectrometry.
  
  
  RESULTS
  Immunoblot analysis revealed that the expression of organic anion transporting polypeptide 1B3 (OATP1B3) and multidrug resistance p-glycoprotein (MDR)-3, as influx and efflux transporters, respectively, were significantly higher in ICG-accumulated HCC (ICG-high HCC) than in ICG-low HCC. ICG was fluorescently observed in the pseudoglands and bile canaliculi abundantly expressing MDR3. An immunohistochemical examination revealed significantly worse disease-free and overall survival rates in patients with MDR3-negative HCC, in which the intratumoral accumulation of some phosphatidylcholine species was observed under imaging mass spectrometry.
  
  
  CONCLUSIONS
  The intratumoral expression of MDR3, a key efflux transporter of ICG, affected the prognosis of patients with HCC, presumably by altering the lipid composition of the lipid bilayers.
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: yasushi.shibasaki@gmail.com.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shibasaki
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Sakaguchi
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Hiraide
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Faculty of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Baba
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism*; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D029362:Organic Anion Transporters, Sodium-Independent; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; C095122:multidrug resistance protein 3; D007208:Indocyanine Green
keywords: Hepatocellular carcinoma; ICG; MDR3; OATP1B3; Transporter