Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma

Authors

  • Atsushi Matsuda,

    1. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan
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  • Atsushi Kuno,

    1. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan
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  • Toru Kawamoto,

    1. Tsukuba Stomach and Intestinal Hospital, Tsukuba, Ibaraki, Japan
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  • Hideki Matsuzaki,

    1. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan
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  • Tatsuro Irimura,

    1. Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
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  • Yuzuru Ikehara,

    1. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan
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  • Yoh Zen,

    1. Department of Human Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
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  • Yasuni Nakanuma,

    1. Department of Human Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
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  • Masakazu Yamamoto,

    1. Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
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  • Nobuhiro Ohkohchi,

    1. Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
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  • Junichi Shoda,

    1. Field of Basic Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
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  • Jun Hirabayashi,

    1. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan
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  • Hisashi Narimatsu

    Corresponding author
    1. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan
    • Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan
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    • fax: +81-29-861-3191


  • Potential conflict of interest: Nothing to report.

Abstract

Cholangiocarcinoma (CC) is an aggressive malignant tumor for which useful markers are not presently available for early and precise diagnosis. The aim of this study was therefore to identify a high-performance diagnostic marker with a special focus on glyco-alteration of glycoproteins. In the course of study, we found that Wisteria floribunda agglutinin (WFA) is the best probe to differentiate intrahepatic cholangiocarcinoma (ICC) lesions from normal bile duct epithelia (BDE) (P < 0.0001). The subsequent histochemical study confirmed ICC-specific WFA staining on 165 tissue specimens. On the other hand, the WFA staining was shown to be closely associated with that of MY.1E12 established previously against sialylated mucin 1 (MUC1) by double-staining experiments. Moreover, glyco-alteration of MUC1 could be verified by western blotting of WFA-captured bile samples from patients with CC patients. Thus, we attempted to construct an enzyme-linked immunosorbent assay system for more convenient CC diagnosis, where WFA-coated plates, the specific monoclonal antibody MY.1E12, and the bile specimens from CC including ICC (n = 30) and benign diseases (n = 38) were combined. As a result, CC was clearly distinguished from benign diseases with statistical scores (sensitivity = 90.0%, specificity = 76.3%, and area under the curve = 0.85). As a particular note, the obtained sensitivity is the highest score among those having been so far reported. Conclusion: Our approach focusing significant glyco-alteration of a particular glycoprotein yielded a novel diagnostic system for CC with satisfactory clinical scores. HEPATOLOGY 2010

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