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Immunohistochemical expression profiles of solute carrier transporters in alpha-fetoprotein-producing gastric cancer.
Shimakata, Takaaki; Kamoshida, Shingo; Kawamura, Jumpei; Ogane, Naoki; Kameda, Yoichi; Yanagita, Emmy; Itoh, Tomoo; Takeda, Risa; Naka, Ayano; Sakamaki, Kuniko; Hayashi, Yurie; Kuwao, Sadahito.
Afiliación
  • Shimakata T; Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
  • Kamoshida S; Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Suma, Kobe, Hyogo, Japan. skamo@harbor.kobe-u.ac.jp.
  • Kawamura J; Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
  • Ogane N; Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Matsuda, Ashigarakami, Kanagawa, Japan.
  • Kameda Y; Department of Pathology, Kanagawa Prefectural Ashigarakami Hospital, Matsuda, Ashigarakami, Kanagawa, Japan.
  • Yanagita E; Department of Diagnostic Pathology, Kobe University Hospital, Chuo, Kobe, Hyogo, Japan.
  • Itoh T; Department of Diagnostic Pathology, Kobe University Hospital, Chuo, Kobe, Hyogo, Japan.
  • Takeda R; Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Suma, Kobe, Hyogo, Japan.
  • Naka A; Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Suma, Kobe, Hyogo, Japan.
  • Sakamaki K; Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
  • Hayashi Y; Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
  • Kuwao S; Division of Diagnostic Pathology and Cytology, Higashiyamato Hospital, Higashiyamato, Tokyo, Japan.
Histopathology ; 69(5): 812-821, 2016 Nov.
Article en En | MEDLINE | ID: mdl-27245475
AIMS: 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. METHODS AND 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 /OAT2high was 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Neoplasias Gástricas / Biomarcadores de Tumor / Resistencia a Antineoplásicos Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Histopathology Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transporte de Membrana / Neoplasias Gástricas / Biomarcadores de Tumor / Resistencia a Antineoplásicos Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Histopathology Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido