Cluster of Differentiation 274 Antigen Immunohistochemical Expression in Tumor and Peri-tumor Cells of Hodgkin and Non-Hodgkin Lymphoma and Clinicopathological Relation (Single-center Study)

Authors

  • Walaa Ghanam Department of Pathology, Faculty of Medicine, Suez University, Suez, Egypt
  • Shaimaa M. M. Bebars Department of Pathology, Faculty of Medicine, Aswan University, Aswan, Egypt https://orcid.org/0000-0001-8415-5824

DOI:

https://doi.org/10.3889/oamjms.2021.7227

Keywords:

Cluster of differentiation 274 antigen, Classic Hodgkin lymphoma, Diffuse large B cell lymphoma, Immunohistochemistry, Non-Hodgkin lymphoma, Programmed cell death protein 1

Abstract

BACKGROUND: Cluster of differentiation 274 (CD274) antigen has been investigated in tumors to evaluate its regulation and effect as a predictive of targeted therapy. Its expression and effect in lymphoma have raised interest recently. However, results were mixed and showed wide variations.

AIM: This study aims to explore and compare CD274 antigen immunohistochemical expression in tumor and peri-tumor cells of classic Hodgkin lymphoma (HL) and diffuse large B cells non-HL (NHL) and its relation with clinicopathological criteria.

METHODS: This work was carried out on 78 cases of lymph node excision biopsy (48 HL and 30 NHL). Prepared sections were applied for immunohistochemistry using CD274 monoclonal rabbit anti-human (programmed cell death protein 1 [PD-L1] ZR3-ASR, a Sigma Aldrich company). Assessment of CD274 antigen in tumor cells was considered positive if detected in >10% (membranous staining with cytoplasmic accentuation). Peri-tumor cells were scored as: 0, no positive cells/high-power field (HPF); 1, <10 positive cells/HPF; 2, 10–30 positive cells/HPF; 3, >30 positive cells/HPF.

RESULTS: CD274 antigen was expressed in 53.8% of total lymphoma cases with significantly more expression of CD274 antigen in HL than NHL (66.7% vs. 33.3%). Classic HL showed significantly higher expression of CD274 antigen in tumor and peri-tumor cells and significant association with elevated erythrocyte sedimentation rate and lactate dehydrogenase and male gender.

INTERPRETATION AND CONCLUSION: There is a more frequent and significant expression of CD274 antigen in classic HL than NHL cases in tumor and peri-tumor cells and a significant association with bad prognostic criteria in classic HL. High expression of CD274 antigen in classic HL proposes its potential use as a marker, especially for prognostic indication.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887-95. PMid:1396582 DOI: https://doi.org/10.1002/j.1460-2075.1992.tb05481.x

Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361-70. http://doi.org/10.1158/2326-6066.CIR-13-0127 PMid:24764583 DOI: https://doi.org/10.1158/2326-6066.CIR-13-0127

Faraj SF, Munari E, Guner G, Taube J, Anders R, Hicks J, et al. Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology. 2015;85(3):703. e1-6. http://doi.org/10.1016/j.urology.2014.10.020 PMid:25733301 DOI: https://doi.org/10.1016/j.urology.2014.10.020

Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255-65. DOI: https://doi.org/10.1016/S0140-6736(16)32517-X

Herbst RS, Soria J, Kowanetz M, Fine GD, Hamid O, Kohrt HE, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A. Nature. 2014;515(7528):563-7. http://doi.org/10.1038/nature14011 Mid:25428504 DOI: https://doi.org/10.1038/nature14011

Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847-56. http://doi.org/10.1158/1535-7163.MCT-14-0983 Mid:25695955 DOI: https://doi.org/10.1158/1535-7163.MCT-14-0983

Miranda-Filho A, Piñeros M, Znaor A, Marcos-Gragera R, Steliarova-Foucher E, Bray F. Global patterns and trends in the incidence of non-Hodgkin lymphoma. Cancer Causes Control. 2019;30(5):489-99. http://doi.org/10.1007/s10552-019-01155-5 PMid:30895415 DOI: https://doi.org/10.1007/s10552-019-01155-5

Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018;50(1):74-87. http://doi.org/10.1016/j.pathol.2017.09.006 PMid:29167021 DOI: https://doi.org/10.1016/j.pathol.2017.09.006

Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82. http://doi.org/10.1182/blood-2003-05-1545 PMid:14504078 DOI: https://doi.org/10.1182/blood-2003-05-1545

Chan A, Dogan A. Prognostic and predictive biomarkers in diffuse large B-cell lymphoma. Surg Pathol Clin. 2019;12(3):699-707. http://doi.org/10.1016/j.path.2019.03.012 PMid:31352982 DOI: https://doi.org/10.1016/j.path.2019.03.012

Zhou L, Deng Y, Li N, Zheng Y, Tian T, Zhai Z, et al. Global, regional, and national burden of Hodgkin lymphoma from 1990 to 2017: Estimates from the 2017 global burden of disease study. J Hematol Oncol. 2019;12(1):107. http://doi.org/10.1186/s13045-019-0799-1 PMid:31640759 DOI: https://doi.org/10.1186/s13045-019-0799-1

World Health Organization. IARC, Egypt, Globocan 2020, (n.d.). Available from: https://gco.iarc.fr/today/data/factsheets/populations/818-egypt-fact-sheets.pdf [Last accessed on 2021 May 22].

Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol. 2018;93(5):704-15. http://doi.org/10.1002/ajh.25071 PMid:29634090 DOI: https://doi.org/10.1002/ajh.25071

Li Y, Wang J, Li C, Ke XY. Contribution of PD-L1 to oncogenesis of lymphoma and its RNAi-based targeting therapy. Leuk Lymphoma. 2012;53(10):2015-23. http://doi.org/10.3109/10428194.2012.673228 PMid:22462616 DOI: https://doi.org/10.3109/10428194.2012.673228

Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, et al. PD-L1 expression is characteristic of a subset of aggressive B cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2014;19(13):3462-73. http://doi.org/10.1158/1078-0432.CCR-13-0855 PMid:23674495 DOI: https://doi.org/10.1158/1078-0432.CCR-13-0855

Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, et al. Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood. 2015;126(19):2193-201. http://doi.org/10.1182/blood-2015-02-629600 PMid:26239088 DOI: https://doi.org/10.1182/blood-2015-02-629600

Menter T, Bodmer-Haecki A, Dirnhofer S, Tzankov A. Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin and B-cell lymphomas. Hum Pathol. 2016;54:17-24. http://doi.org/10.1016/j.humpath.2016.03.005 PMid:27045512 DOI: https://doi.org/10.1016/j.humpath.2016.03.005

Glinsmann-Gibson B, Wisner L, Stanton M, Larsen B, Rimsza L, Maguire A. Recommendations for tissue microarray construction and quality assurance. Appl Immunohistochem Mol Morphol. 2019;28(4):325-330. http://doi.org/10.1097/PAI.0000000000000739 PMid:31033496 DOI: https://doi.org/10.1097/PAI.0000000000000739

Kwon D, Kim S, Kim PJ, Go H, Nam SJ, Paik JH, et al. Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas. Histopathology. 2016;68(7):1079-89. http://doi.org/10.1111/his.12882 PMid:26426431 DOI: https://doi.org/10.1111/his.12882

Caponetti G, Bagg A. Demystifying the diagnosis and classification of lymphoma: A hematologist/oncologist’s guide to the hematopathologist’s galaxy. J Community Support Oncol. 2017;15(1):43-8.

Bröckelmann PJ, Eichenauer DA, Jakob T, Follmann M, Engert A, Skoetz N. Hodgkin lymphoma in adults diagnosis, treatment, and follow-up. Dtsch Arztebl Int. 2018;115(31-32):535-40. http://doi.org/10.3238/arztebl.2018.0535 PMid:30149835 DOI: https://doi.org/10.3238/arztebl.2018.0535

Herzog CM, Dey S, Hablas A, Khaled HM, Seifeldin IA, Ramadan M, et al. Geographic distribution of hematopoietic cancers in the nile delta of Egypt. Ann Oncol. 2012;23(10):2748-55. http://doi.org/10.1093/annonc/mds079 PMid:22553197 DOI: https://doi.org/10.1093/annonc/mds079

Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 2019;12(1):92. http://doi.org/10.1186/s13045-019-0779-5 PMid:31488176 DOI: https://doi.org/10.1186/s13045-019-0779-5

Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci Transl Med. 2016;8(328):328rv4. http://doi.org/10.1126/scitranslmed.aad7118 PMid:26936508 DOI: https://doi.org/10.1126/scitranslmed.aad7118

Ghosh C, Luong G, Sun Y. A snapshot of the PD-1/PD-L1 pathway. J Cancer. 2021;12(9):2735-46. http://doi.org/10.7150/jca.57334 PMid:33854633 DOI: https://doi.org/10.7150/jca.57334

Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Bin CY, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large b-cell lymphoma: Results of an international phase II trial. J Clin Oncol. 2013;31(33):4199-206. http://doi.org/10.1200/JCO.2012.48.3685 PMid:24127452 DOI: https://doi.org/10.1200/JCO.2012.48.3685

Panjwani PK, Charu V, DeLisser M, Molina-Kirsch H, Natkunam Y, Zhao S. Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes. Hum Pathol. 2018;71:91-9. http://doi.org/10.1016/j.humpath.2017.10.029 PMid:29122656 DOI: https://doi.org/10.1016/j.humpath.2017.10.029

Vranic S, Ghosh N, Kimbrough J, Bilalovic N, Bender R, Arguello D, et al. PD-L1 status in refractory lymphomas. PLoS One. 2016;11(11):e0166266. http://doi.org/10.1371/journal.pone.0166266 PMid:27861596 DOI: https://doi.org/10.1371/journal.pone.0166266

Xing W, Dresser K, Zhang R, Evens AM, Yu H, Woda BA, et al. PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: Clinicopathologic features and prognostic implications. Oncotarget. 2016;7(37):59976-86. http://doi.org/10.18632/oncotarget.11045 PMid:27527850 DOI: https://doi.org/10.18632/oncotarget.11045

Taylor JG, Clear AJ, Truelove E, Calaminici M, Gribben JG. Beyond exhaustion: The PDL1-PD1 axis shapes the classical hodgkin lymphoma microenvironment. Blood. 2019;134(Suppl 1):658-8. DOI: https://doi.org/10.1182/blood-2019-125247

Gravelle P, Burroni B, Péricart S, Rossi C, Bezombes C, Tosolini M, et al. Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: A summary of immunohistochemical studies. Oncotarget. 2017;8(27):44960-75. http://doi.org/10.18632/oncotarget.16680 PMid:28402953 DOI: https://doi.org/10.18632/oncotarget.16680

Wei Y, Xiao X, Lao XM, Zheng L, Kuang DM. Immune landscape and therapeutic strategies: New insights into PD-L1 in tumors. Cell Mol Life Sci. 2021;78(3):867-87. http://doi.org/10.1007/s00018-020-03637-1 Mid:32940722 DOI: https://doi.org/10.1007/s00018-020-03637-1

Ozuah NW, LaCasce AS. Clinical evaluation and management of hodgkin lymphoma. In: Concise Guide to Hematology. Berlin, Heidelberg: Springer International Publishing; 2019. p. 371-8. DOI: https://doi.org/10.1007/978-3-319-97873-4_30

Downloads

Published

2021-10-23

How to Cite

1.
Ghanam W, Bebars SMM. Cluster of Differentiation 274 Antigen Immunohistochemical Expression in Tumor and Peri-tumor Cells of Hodgkin and Non-Hodgkin Lymphoma and Clinicopathological Relation (Single-center Study). Open Access Maced J Med Sci [Internet]. 2021 Oct. 23 [cited 2024 Mar. 29];9(A):1011-8. Available from: https://oamjms.eu/index.php/mjms/article/view/7227