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A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status

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Abstract

Gallbladder cancer (GBC) has a poor prognosis, and new targeted therapeutic options are needed. We investigated the human epidermal growth factor receptor 2 (HER2) status and its clinicopathological significance in a large cohort of GBC patients. We assessed HER2 expression in a consecutive series of 211 GBC cases by immunohistochemistry (IHC), paying particular attention to intratumoral heterogeneity. HER2 gene amplification was analyzed by dual-color fluorescence in situ hybridization (FISH). An HER2 positive status was called when the IHC score was 3+ or when the IHC score was 2+, and FISH was positive. Correlations were analyzed between HER2 status and clinicopathological parameters including survival. The HER2 IHC score was 0 in 144 (68.2 %), 1+ in 28 (13.3 %), 2+ in 14 (6.6 %), and 3+ in 25 cases (11.8 %). In 20/39 (51 %) of the IHC 2+ and 3+ cases, the staining pattern was heterogeneous. In HER2 IHC score 2+ and 3+ cases, HER2 FISH was positive in 83 % (10/12) and 96 % (24/25), respectively. Altogether, 35/211 cases (16.6 %) were HER2 positive. There was no significant association between HER2 status and clinicopathological variables or survival. We identified a significant subgroup of HER2-positive GBC cases, for whom a clinical trial with anti-HER2 therapy might be considered.

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Acknowledgments

This study was supported by the National Cancer Center Research and Development Fund. We thank Sachiko Miura, M.T.; Toshiko Sakazaki, M. T.; Chizu Kina, M.T.; and Susumu Wakai, M.T., for their technical assistance.

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Authors and Affiliations

  1. Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hiroshi Yoshida & Nobuyoshi Hiraoka

  2. Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Kazuaki Shimada & Tomoo Kosuge

Authors
  1. Hiroshi Yoshida
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  2. Kazuaki Shimada
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  3. Tomoo Kosuge
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  4. Nobuyoshi Hiraoka
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Corresponding author

Correspondence to Nobuyoshi Hiraoka.

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All study participants provided informed consent, and the present study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and with approval of the Institutional Review Board of the National Cancer Center, Tokyo, Japan.

Conflict of interest

The authors declare that they have no competing interests.

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Yoshida, H., Shimada, K., Kosuge, T. et al. A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status. Virchows Arch 468, 431–439 (2016). https://doi.org/10.1007/s00428-015-1898-1

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  • DOI: https://doi.org/10.1007/s00428-015-1898-1

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