Medical Oncology

, 36:23 | Cite as

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

  • Yosuke HirotsuEmail author
  • Hitoshi Mochizuki
  • Kenji Amemiya
  • Hiroshi Ohyama
  • Dai Yoshimura
  • Hiroyuki Amano
  • Yuko Miura
  • Hiroshi Ashizawa
  • Keiko Nakagomi
  • Shinya Takaoka
  • Kenji Hosoda
  • Yoji Suzuki
  • Toshio Oyama
  • Masao Hada
  • Yuichiro Kojima
  • Masao Omata
Original Paper


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.


Microsatellite instability Signet ring cell Non-signet ring cell Gastric cancer Immune checkpoint inhibitor 



Signet ring cell


Mismatch repair


Non-signet ring cell


The Cancer Genome Atlas


Programmed death 1


Programmed death 1 ligand 1


Deficient mismatch repair


Microsatellite instability




Microsatellite instability-high


Microsatellite stable



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 ( for editing a draft of this manuscript.


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.).

Compliance with ethical standards

Conflict of interest

All authors declare no competing interests.

Ethical approval

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.

Informed consent

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

Supplementary material

12032_2019_1246_MOESM1_ESM.doc (32 kb)
Supplementary material 1 (DOC 32 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yosuke Hirotsu
    • 1
    Email author
  • Hitoshi Mochizuki
    • 1
    • 2
  • Kenji Amemiya
    • 1
  • Hiroshi Ohyama
    • 1
    • 2
    • 3
  • Dai Yoshimura
    • 2
  • Hiroyuki Amano
    • 2
  • Yuko Miura
    • 2
  • Hiroshi Ashizawa
    • 2
  • Keiko Nakagomi
    • 2
  • Shinya Takaoka
    • 2
  • Kenji Hosoda
    • 2
  • Yoji Suzuki
    • 2
  • Toshio Oyama
    • 4
  • Masao Hada
    • 5
  • Yuichiro Kojima
    • 2
  • Masao Omata
    • 1
    • 2
    • 6
  1. 1.Genome Analysis CenterYamanashi Central HospitalKofuJapan
  2. 2.Department of GastroenterologyYamanashi Central HospitalKofuJapan
  3. 3.Department of Gastroenterology, Graduate School of MedicineChiba UniversityChibaJapan
  4. 4.Department of PathologyYamanashi Central HospitalKofuJapan
  5. 5.Department of SurgeryYamanashi Central HospitalKofuJapan
  6. 6.University of TokyoTokyoJapan

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