title: Immunohistochemical expression profiles of solute carrier transporters in alpha-fetoprotein-producing gastric cancer.
abstract: OBJECTIVE
  Alpha-fetoprotein (AFP)-producing gastric cancer (GC) is an aggressive tumour with high rates of liver metastasis and poor prognosis, and for which a validated chemotherapy regimen has not been established. Drug uptake by solute carrier (SLC) transporters is proposed as one of the mechanisms involved in sensitivity to chemotherapy. In this study, we aimed to develop important insights into effective chemotherapeutic regimens for AFP-producing GC.
  
  
  RESULTS
  We evaluated immunohistochemically the expression levels of a panel of SLC transporters in 20 AFP-producing GCs and 130 conventional GCs. SLC transporters examined were human equilibrative nucleoside transporter 1 (hENT1), organic anion transporter 2 (OAT2), organic cation transporter (OCT) 2, OCT6 and organic anion-transporting polypeptide 1B3 (OATP1B3). The rates of high expression levels of hENT1 (hENT1high) and OAT2 (OAT2high) were statistically higher in AFP-producing GC, compared with conventional GC. When analysing hENT1 and OAT2 in combination, hENT1high/OAT2highwas the most particular expression profile for AFP-producing GC, with a greater significance than hENT1 or OAT2 alone. However, no significant differences in OCT2, OCT6 or OATP1B3 levels were detected between AFP-producing and conventional GCs. However, immunoreactivity for hENT1, OAT2 and OCT6 tended to be increased in GC tissues compared with non-neoplastic epithelia.
  
  
  CONCLUSIONS
  Because hENT1 and OAT2 are crucial for the uptake of gemcitabine and 5-fluorouracil, respectively, our results suggest that patients with AFP-producing GC could potentially benefit from gemcitabine/fluoropyrimidine combination chemotherapy. Increased expression of hENT1, OAT2 and OCT6 may also be associated with the progression of GC.
authors.affiliation: Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shimakata
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Suma, Kobe, Hyogo, Japan. skamo@harbor.kobe-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
authors.affiliation: Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Kawamura
authors.affiliation: Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Matsuda, Ashigarakami, Kanagawa, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ogane
authors.affiliation: Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Matsuda, Ashigarakami, Kanagawa, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.affiliation: Department of Diagnostic Pathology, Kobe University Hospital, Chuo, Kobe, Hyogo, Japan.
authors.forename: Emmy
authors.initials: E
authors.lastname: Yanagita
authors.affiliation: Department of Diagnostic Pathology, Kobe University Hospital, Chuo, Kobe, Hyogo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Suma, Kobe, Hyogo, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Takeda
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Suma, Kobe, Hyogo, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Naka
authors.affiliation: Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Sakamaki
authors.affiliation: Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
authors.forename: Sadahito
authors.initials: S
authors.lastname: Kuwao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000378:metabolism*; D059467:Transcriptome; D000509:alpha-Fetoproteins / Q000096:biosynthesis
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D026901:Membrane Transport Proteins; D000509:alpha-Fetoproteins
keywords: alpha-fetoprotein; gastric cancer; human equilibrative nucleoside transporter 1; organic anion transporter 2; solute carrier transporter