Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma

  • Eri IshikawaEmail author
  • Masanao Nakamura
  • Kazuyuki Shimada
  • Tsutomu Tanaka
  • Akira Satou
  • Kei Kohno
  • Ayako Sakakibara
  • Kazuhiro Furukawa
  • Takeshi Yamamura
  • Ryoji Miyahara
  • Shigeo Nakamura
  • Seiichi Kato
  • Mitsuhiro Fujishiro
Original Article—Alimentary Tract



Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the most common gastrointestinal lymphoma. The prognostic/predictive indicators among patients with gastric and intestinal DLBCL (giDLBCL) are controversial beyond their anatomical sites. We compared giDLBCL cases and investigated the clinical utility of newly emerging indicators with an emphasis on programmed cell death ligand 1 (PD-L1) expression.


This retrospective study included 174 patients with primary gastric (n = 129) or intestinal (n = 45) DLBCL treated with rituximab-containing chemotherapy between 1995 and 2018.


Compared with gastric DLBCL (gDLBCL) cases, patients with intestinal DLBCL (iDLBCL) had a significantly higher rate of advanced Lugano stage (71% vs 37%, P < 0.001), perforation (13% vs. 0.8%, P = 0.001), PD-L1 expression on microenvironment immune cells (miPD-L1, 70% vs 46%, P = 0.008), CD10 positivity (47% vs 28%, P = 0.027), and CD5 positivity (9% vs 1.6%, P = 0.040). The iDLBCL patients showed significantly worse progression-free survival (PFS) and overall survival (OS) than gDLBCL cases (P = 0.0338 and P = 0.0077, respectively). PD-L1 expression on tumor cells was detected in only 3 (2%) of 174 cases with early relapse and/or an aggressive clinical course; whereas, miPD-L1-positive cases had significantly better OS than the miPD-L1-negative gDLBCL and iDLBCL cases (P = 0.0281 and P = 0.0061, respectively). Multivariate analysis revealed that miPD-L1 negativity (P = 0.030) was an independent adverse prognostic factor for OS in giDLBCL.


The anatomical site of disease did not influence outcome in giDLBCL cases treated with rituximab-containing chemotherapy; while, miPD-L1 expression had a favorable impact on the outcome.


DLBCL PD-L1 Gastric lymphoma Intestinal lymphoma Gastrointestinal lymphoma 



Complete remission


Died of disease


Diffuse large B-cell lymphoma


Died of other causes


Epstein-Barr virus-encoded small RNA


Epstein-Barr virus


Gastric diffuse large B-cell lymphoma


Gastric and intestinal diffuse large B-cell lymphoma


Intestinal diffuse large B-cell lymphoma


Lactate dehydrogenase


Programmed cell death ligand 1 expression on microenvironment immune cells


No evidence of disease


Recurrence of disease at 24 months or later


Programmed cell death ligand 1 expression on neoplastic cells


Overall survival


Programmed cell death ligand 1


Progression-free survival

R-containing chemotherapy

Rituximab-containing chemotherapy


Recurrence of disease within 24 months



The authors thank Y. Katayama, Y. Inagaki, K. Matsubara, and K. Kito for technical assistance and the following collaborators for providing patient clinical data and specimens: Aichi Cancer Center Hospital, Anjo Kosei Hospital, Ekisaikai Hospital, Fujita Health University, Ishikawa Prefectural Central Hospital, Japanese Red Cross Nagoya Daini Hospital, Kani Tono Hospital, Kariya Toyota General Hospital, Koseiren Takaoka Hospital, Matsue City Hospital, Ogaki Municipal Hospital, Okazaki Municipal Hospital, Omihachiman Community Medical Center, Shizuoka Saiseikai General Hospital, Suzuka Chuo General Hospital, Takatsuki General Hospital, Toyota Kosei Hospital, Toyota Memorial Hospital, Toyama Prefectural Central Hospital, Toyohashi Medical center, and Toyohashi Municipal Hospital.

Author contributions

EI, SN, and MF: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, revision of the manuscript, statistical analysis. SK, KS, AS, and KK: acquisition of data, analysis and interpretation of data. Rest of authors: acquisition of data. All authors approved the final version of the manuscript.



Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2019_1616_MOESM1_ESM.docx (29 kb)
Supplementary file1 (DOCX 29 kb)
535_2019_1616_MOESM2_ESM.tif (5.2 mb)
Supplementary file2 (TIF 5303 kb)


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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  • Eri Ishikawa
    • 1
    • 2
    Email author
  • Masanao Nakamura
    • 1
  • Kazuyuki Shimada
    • 3
  • Tsutomu Tanaka
    • 4
  • Akira Satou
    • 5
  • Kei Kohno
    • 2
  • Ayako Sakakibara
    • 2
  • Kazuhiro Furukawa
    • 1
  • Takeshi Yamamura
    • 6
  • Ryoji Miyahara
    • 1
  • Shigeo Nakamura
    • 2
  • Seiichi Kato
    • 7
  • Mitsuhiro Fujishiro
    • 1
  1. 1.Department of Gastroenterology and HepatologyNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Pathology and Laboratory MedicineNagoya University HospitalNagoyaJapan
  3. 3.Department of Hematology and OncologyNagoya University Graduate School of MedicineNagoyaJapan
  4. 4.Department of EndoscopyAichi Cancer Center HospitalNagoyaJapan
  5. 5.Department of Surgical PathologyAichi Medical University HospitalNagakuteJapan
  6. 6.Department of EndoscopyNagoya University HospitalNagoyaJapan
  7. 7.Department of Pathology and Molecular DiagnosticsAichi Cancer Center HospitalNagoyaJapan

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