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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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

DLBCL PD-L1 Gastric lymphoma Intestinal lymphoma Gastrointestinal lymphoma 

Abbreviations

CR

Complete remission

DD

Died of disease

DLBCL

Diffuse large B-cell lymphoma

DOC

Died of other causes

EBER

Epstein-Barr virus-encoded small RNA

EBV

Epstein-Barr virus

gDLBCL

Gastric diffuse large B-cell lymphoma

giDLBCL

Gastric and intestinal diffuse large B-cell lymphoma

iDLBCL

Intestinal diffuse large B-cell lymphoma

LDH

Lactate dehydrogenase

miPD-L1

Programmed cell death ligand 1 expression on microenvironment immune cells

NED

No evidence of disease

non-ROD24

Recurrence of disease at 24 months or later

nPD-L1

Programmed cell death ligand 1 expression on neoplastic cells

OS

Overall survival

PD-L1

Programmed cell death ligand 1

PFS

Progression-free survival

R-containing chemotherapy

Rituximab-containing chemotherapy

ROD24

Recurrence of disease within 24 months

Notes

Acknowledgements

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.

Funding

None.

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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