Gastric Cancer

, Volume 22, Issue 4, pp 785–792 | Cite as

Predictive value of MLH1 and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer

  • Tadayoshi Hashimoto
  • Yukinori KurokawaEmail author
  • Tsuyoshi Takahashi
  • Yasuhiro Miyazaki
  • Koji Tanaka
  • Tomoki Makino
  • Makoto Yamasaki
  • Kiyokazu Nakajima
  • Jun-ichiro Ikeda
  • Masaki Mori
  • Yuichiro Doki
Original Article



Microsatellite instability (MSI) and programmed death-ligand 1 (PD-L1) are candidate predictors for the response to immune checkpoint inhibitors, and may predict chemotherapy sensitivity. We investigated the simultaneous expression of mutL homolog 1 (MLH1), a mismatch repair gene, and PD-L1 in gastric cancers.


We examined MLH1 and PD-L1 expression in surgical specimens from 285 gastric cancer patients treated with or without preoperative chemotherapy, and assessed the relation between expression results and both histological response and recurrence-free survival (RFS).


Of 285 patients, 28 (9.8%) and 70 (24.6%) exhibited negative MLH1 and high PD-L1 expression, respectively. Most MLH1-negative tumors (85.7%) showed high MSI, and these tumors exhibited high PD-L1 expression more frequently than MLH1-positive tumors (57.1% vs. 21.0%, P < 0.001). MLH1-negative patients were significantly less likely to respond to preoperative chemotherapy than MLH1-positive patients (16.7% vs. 61.2%, P = 0.005), whereas there was no significant difference between high- and low-PD-L1 expression patients (55.9% vs. 56.6%, P = 0.95). RFS in patients without preoperative chemotherapy was significantly longer in the MLH1-negative group than in the MLH1-positive group (HR 0.30; 95% CI 0.09–0.95; P = 0.030), whereas in patients with preoperative chemotherapy there was no significant difference in RFS between the two groups (HR 0.70; 95% CI 0.30–1.63; P = 0.41). PD-L1 expression was not associated with RFS in patients with or without chemotherapy.


Loss of MLH1 was associated with chemoresistance and did not prolong survival following neoadjuvant chemotherapy. The strong association between MLH1 and MSI status suggests that immune checkpoint inhibitors may be preferable to conventional chemotherapy for MLH1-negative gastric cancer.


MutL homolog 1 Programmed death-ligand 1 Mismatch repair deficient Microsatellite instability Neoadjuvant chemotherapy 



The authors declare that this study was not funded.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical standards

Written informed consent was obtained from all patients prior to the procedure. The study was approved by the ethics committee of the Institutional Review Board.


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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

Authors and Affiliations

  • Tadayoshi Hashimoto
    • 1
  • Yukinori Kurokawa
    • 1
    Email author
  • Tsuyoshi Takahashi
    • 1
  • Yasuhiro Miyazaki
    • 1
  • Koji Tanaka
    • 1
  • Tomoki Makino
    • 1
  • Makoto Yamasaki
    • 1
  • Kiyokazu Nakajima
    • 1
  • Jun-ichiro Ikeda
    • 2
  • Masaki Mori
    • 3
  • Yuichiro Doki
    • 1
  1. 1.Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Department of PathologyOsaka University Graduate School of MedicineOsakaJapan
  3. 3.Department of Surgery and ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan

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