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Claudins-4 and -7 might be valuable markers to distinguish hepatocellular carcinoma from cholangiocarcinoma

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Abstract

The claudin family members are the functional components of tight junctions. Expression and localization of claudins vary among organs and tumor types. In this study, we examined expression and localization of tight junction proteins (TJP) in human liver tumors, to estimate their usefulness as differential diagnostic markers. The materials used for immunohistochemical analysis were 47 liver tumor specimens including 29 cases of hepatocellular carcinoma (HCC), 15 cases of cholangiocarcinoma (CC), 3 cases of combined HCC and CC (CHC), and 3 cases of cholangiolocellular carcinoma (CoCC). Samples were examined using semiquantitative and statistical analysis of immunoreactivity. In HCC, claudin-1, occludin, tricellulin, and JAM-A were expressed on the cell membrane as well as in hepatocytes. In CC, claudins-1, -4, and -7, tricellulin, and JAM-A were expressed on the cell membrane and occludin was predominantly expressed in the apicalmost areas of the cell membrane. Significant differences in the immunohistochemical scores of claudin-4 and claudin-7 were observed when comparing HCC and CC. CHC was positive for all of the TJPs examined in this study. The expression pattern of CoCC was found to be similar to that of CC. There were differences in the distribution of intensity scores of claudins-4 and -7 and occludin between CoCC and HCC. In addition, CHC was positive for Glypican-3 and CK-19. CoCC was positive for only CK-19. The results suggest that claudins-4 and -7 might be valuable markers for distinguishing HCC and CC and that CoCC might arise from hepatic ductal cells.

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Acknowledgments

This work was supported in by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare of Japan.

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    Authors and Affiliations

    1. Department of Pathology, Sapporo Medical University School of Medicine, S1. W17, Sapporo, 060-8556, Japan

      Yusuke Ono, Yutaro Hiratsuka, Masaki Murata, Akira Takasawa, Rieko Fukuda, Satoshi Tanaka, Makoto Osanai & Norimasa Sawada

    2. Division of Advanced Medicine Promotion, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

      Masanori Nojima

    3. Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

      Koichi Hirata

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    1. Yusuke Ono
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    Correspondence to Masaki Murata.

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    Yusuke Ono and Yutaro Hiratsuka contributed equally to this work.

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    Ono, Y., Hiratsuka, Y., Murata, M. et al. Claudins-4 and -7 might be valuable markers to distinguish hepatocellular carcinoma from cholangiocarcinoma. Virchows Arch 469, 417–426 (2016). https://doi.org/10.1007/s00428-016-1984-z

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    • DOI: https://doi.org/10.1007/s00428-016-1984-z

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