For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
7
views
23
references
 Top references
cited by
30
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      123
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2‐negative status

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Gastric cancer ( GC) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death‐1 ( PD‐1)/programmed death‐ligand 1 ( PD‐L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of PD‐L1 and its prognostic value in GC. We aimed to evaluate the expression rates of PD‐L1 in GC, and further assess its relationship with mismatch repair ( MMR), and human epidermal growth factor receptor 2 ( HER2) status. We retrospectively collected 550 consecutive cases of GC in Fudan University Shanghai Cancer Center from 2010 to 2012. PD‐L1, MMR protein, and HER2 status were detected by immunohistochemistry ( IHC). Fluorescence in situ hybridization was further used in HER2 IHC 2+ cases. Cases with at least 1% membranous and/or cytoplasmic PD‐L1 staining in either tumor cells ( TCs) or tumor‐infiltrating immune cells ( TIICs) were considered as PD‐L1 positive. The correlation between clinicopathological parameters, HER2, MMR, and PD‐L1 expression status was determined using chi‐squared tests. About 37.3% cases (205/550) showed PD‐L1 expression in TCs and/or TIICs. 17.3% cases (95/550) showed PD‐L1 expression in TCs, 34.5% (190/550) cases showed PD‐L1 expression in TIICs. There were 45 deficient MMR ( dMMR) cases (8.2%), which showed higher rates of PD‐L1 expression compared with MMR‐proficient carcinomas (60.0% vs. 35.2%, P = 0.001). HER2 was positive in 66 (12.0%) cases. The expression of PD‐L1 occurred more frequently in HER2‐negative group than HER2‐positive cohorts (39.0% vs. 24.2%, P = 0.020). The survival analysis revealed that PD‐L1 was not associated with prognosis. This study evaluated the association between the PD‐L1 expression and a specific subgroup ( dMMR and HER2‐negative) in a large Asian cohort of GC. GC patients with dMMR and HER2‐negative status exhibited higher PD‐L1 expression rates. Our finding indicated that MMR and HER‐2 status might be potential biomarkers for anti‐ PD‐L1 therapy.

          Related collections

          Most cited references23

          • Record: found
          • Abstract: found
          • Article: not found

          Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma.

          Elizabeth Thompson, Marianna Zahurak, Adrian Murphy … (2017)
          Recent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. Here, we evaluate gastric and gastro-oesophageal junction (G/GEJ) adenocarcinomas for their expression of programmed death-ligand 1 (PD-L1), infiltration by CD8+ T cells and the relationship of both factors to patient survival.
          Article 0 comments Cited 219 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer

            Eric Van Cutsem, Yung-Jue Bang, Feng Feng-yi … (2014)
            Background In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors. Methods HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed. Results The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %. Conclusions HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to. Electronic supplementary material The online version of this article (doi:10.1007/s10120-014-0402-y) contains supplementary material, which is available to authorized users.
            Article 0 comments Cited 198 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma.

              Junichi Kiyasu, Hiroaki Miyoshi, Akie Hirata … (2015)
              Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1(+) DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1(+) DLBCL. We also defined the criteria for microenvironmental PD-L1(+) (mPD-L1(+)) DLBCL (ie, PD-L1(-) DLBCL in which PD-L1(+) nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1(+) tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1(+) and mPD-L1(+) DLBCL were 11% and 15.3%, respectively. Both PD-L1(+) and mPD-L1(+) DLBCL were significantly associated with non-germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1(+) TILs was significantly higher in GCB-type tumors and lower in mPD-L1(-) and PD-L1(+) DLBCL. Patients with PD-L1(+) DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1(-) DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1(+) and mPD-L1(-) DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1(+) DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup.
              Article 0 comments Cited 196 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Weiqi Sheng: shengweiqi2006@163.com
                Journal
                Journal ID (nlm-ta): Cancer Med
                Journal ID (iso-abbrev): Cancer Med
                Journal ID (doi): 10.1002/(ISSN)2045-7634
                Journal ID (publisher-id): CAM4
                Title: Cancer Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2045-7634
                Publication date (Electronic): 19 April 2018
                Publication date Collection: June 2018
                Volume: 7
                Issue: 6 ( doiID: 10.1002/cam4.2018.7.issue-6 )
                Pages: 2612-2620
                Affiliations
                [ 1 ] Department of Pathology Fudan University Shanghai Cancer Center Shanghai 200032 China
                [ 2 ] Department of Oncology Shanghai Medical College Fudan University Shanghai 200032 China
                Author notes
                [*] [* ] Correspondence

                Weiqi Sheng, Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, China. Tel: +86‐21‐64175590; Fax: +86‐21‐64174774; E‐mail: shengweiqi2006@ 123456163.com

                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-9093-3418
                Article
                Publisher ID: CAM41502
                DOI: 10.1002/cam4.1502
                PMC ID: 6010739
                PubMed ID: 29673110
                SO-VID: a313aa70-f3d9-457e-b59b-4444ee2050bd
                Copyright © © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 January 2018
                Date revision received : 21 March 2018
                Date accepted : 22 March 2018
                Page count
                Figures: 4, Tables: 3, Pages: 9, Words: 6052
                Funding
                Funded by: Natural Science Foundation of Shanghai
                Award ID: 17ZR1406500
                Funded by: National Natural Science Foundation of China
                Award ID: 81201898
                Funded by: Shanghai hospital development center Emerging advanced technology joint research project
                Award ID: HDC12014105
                Funded by: Shanghai Key Developing Disciplines
                Award ID: 2015ZB0201
                Categories
                Subject: Original Research
                Subject: Cancer Biology
                Subject: Original Research
                Custom metadata
                source-schema-version-number 2.0
                component-id cam41502
                cover-date June 2018
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.1.1 mode:remove_FC converted:20.06.2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gastric cancer,her2,mismatch repair deficiency,programmed death‐ligand 1
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: gastric cancer, her2, mismatch repair deficiency, programmed death‐ligand 1

                Comments

                Comment on this article

                scite_

                Similar content123

                See all similar

                Cited by30

                See all cited by

                Most referenced authors911

                See all reference authors