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Deficiency of mismatch repair genes is less frequently observed in signet ring cell compared with non-signet ring cell gastric cancer

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Abstract

Signet ring cell (SRC) gastric cancer at advanced stage has poor prognosis. While a recent study reported nearly one-third of SRC cases contain tumors with deficient mismatch repair (MMR) genes, other studies in SRC have been inconclusive. To re-analyze the results, we performed immunohistochemical staining of MLH1, MSH2, MSH6 and PMS2 proteins in 38 SRC gastric tumors compared with 109 non-SRC (NSRC) tumors from 94 patients. In contrast to the previous study, all SRC gastric tumors normally expressed MMR proteins, whereas 22 of 109 of NSRC (20%) showed deficient MMR proteins. To reinforce our results, we referred to the Cancer Genome Atlas (TCGA) genomic database and found that only 6 (6%) of 99 samples with diffuse gastric tumors showed deficient MMR, whereas 64 (21%) of 304 in intestinal gastric tumors showed deficient MMR. Our results as well as the TCGA database indicated that MMR genes are infrequently inactivated in SRC gastric cancer. These findings indicate that SRC patients may not be the best candidates for immuno-oncology therapy.

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Abbreviations

SRC:

Signet ring cell

MMR:

Mismatch repair

NSRC:

Non-signet ring cell

TCGA:

The Cancer Genome Atlas

PD-1:

Programmed death 1

PD-L1:

Programmed death 1 ligand 1

dMMR:

Deficient mismatch repair

MSI:

Microsatellite instability

IHC:

Immunohistochemistry

MSI-H:

Microsatellite instability-high

MSS:

Microsatellite stable

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Acknowledgements

We thank Ms. Ritsuko Yokouchi and Ms. Naho Sato for data collection of the registry on all the malignant neoplasms at our hospital. We also thank all medical and ancillary staff of the hospital and the patients for consenting to participate. We thank Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript.

Funding

This study was supported by a Grant-in-Aid for Genome Research Project from Yamanashi Prefecture (to M.O. and Y.H.), The Japan Society for the Promotion of Science (JSPS) KAKENHI Early-Career Scientists (Grant Number JP18K16292 to Y.H.), Research Grant for Young Scholars (to Y.H.), The YASUDA Medical Foundation (to Y.H.) and The Uehara Memorial Foundation (to Y.H.).

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Authors and Affiliations

  1. Genome Analysis Center, Yamanashi Central Hospital, 1-1-1, Fujimi, Kofu, Yamanashi, Japan

    Yosuke Hirotsu, Hitoshi Mochizuki, Kenji Amemiya, Hiroshi Ohyama & Masao Omata

  2. Department of Gastroenterology, Yamanashi Central Hospital, Kofu, Japan

    Hitoshi Mochizuki, Hiroshi Ohyama, Dai Yoshimura, Hiroyuki Amano, Yuko Miura, Hiroshi Ashizawa, Keiko Nakagomi, Shinya Takaoka, Kenji Hosoda, Yoji Suzuki, Yuichiro Kojima & Masao Omata

  3. Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Hiroshi Ohyama

  4. Department of Pathology, Yamanashi Central Hospital, Kofu, Japan

    Toshio Oyama

  5. Department of Surgery, Yamanashi Central Hospital, Kofu, Japan

    Masao Hada

  6. University of Tokyo, Tokyo, Japan

    Masao Omata

Authors
  1. Yosuke Hirotsu
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  2. Hitoshi Mochizuki
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Corresponding author

Correspondence to Yosuke Hirotsu.

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All authors declare no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Hirotsu, Y., Mochizuki, H., Amemiya, K. et al. Deficiency of mismatch repair genes is less frequently observed in signet ring cell compared with non-signet ring cell gastric cancer. Med Oncol 36, 23 (2019). https://doi.org/10.1007/s12032-019-1246-4

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  • DOI: https://doi.org/10.1007/s12032-019-1246-4

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