Immunohistochemical Expression of Programmed Death Ligand 1 in Oral Extranodal Diffuse Large B Cell Lymphoma

Rania Hanafi Mahmoud Said; Fatma F. Hussein; Amal M. El-Deeb

doi:10.1055/s-0042-1747951

European Journal of Dentistry, Table of Contents

CC BY 4.0 · Eur J Dent 2023; 17(02): 424-430
DOI: 10.1055/s-0042-1747951

Original Article

Immunohistochemical Expression of Programmed Death Ligand 1 in Oral Extranodal Diffuse Large B Cell Lymphoma

Authors

Rania Hanafi Mahmoud Said

¹Department of Oral Pathology, Faculty of Dentistry, Suez Canal University, El Salam District Ismailia Governorate, Egypt

²Department of Oral Pathology in Faculty of Dentistry, Umm Al Qura University, Kingdom of Saudi Arabia
Fatma F. Hussein

³Department of Oral Medicine, Oral Diagnosis and Periodontology, Faculty of Dentistry, Minia University, Minya, Menia Governorate, Egypt

⁴Faculty of Dentistry, Umm Al Qura University, Kingdom of Saudi Arabia
Amal M. El-Deeb

²Department of Oral Pathology in Faculty of Dentistry, Umm Al Qura University, Kingdom of Saudi Arabia

⁵Department of Oral Pathology, Faculty of Dentistry, Tanta University, Tanta, Gharbia Governorate, Egypt

Abstract

Objective Lymphomas are the third most common cancer after squamous cell carcinoma and salivary gland tumors. Extranodal diffuse B cell lymphoma (DBCL) represents 30 to 58% of non-Hodgkin's lymphoma. One of the major problems of DBCL is the high likelihood of disease relapse following treatment. A recent trend in the treatment of diffuse large B cell lymphoma (DLBCL) is blockage of an immune checkpoint inhibitor that targets the programmed death of cell ligand 1 receptors (PD-L1). PD-L1 activation results in negative regulatory signals that induce apoptosis and inhibit tumor antigen-specific T cells allowing immune evasion of the tumor.

The aim of this aim is to measure the expression level of PD-L1 on oral tissue samples from DLBCL patients using immunohistochemistry.

Materials and Methods This current study was performed at the Faculty of Dentistry, Tanta University, Egypt. Ethical approval was conducted from Faculty of Dentistry, Tanta University. Tissue samples were collected from 13 patients diagnosed with oral extranodal DLBCL) nongerminal center B cell like subtype. Both hematoxylin and eosin and immunohistochemical staining (The avidin-biotin-complex procedure) was performed with anti-PD-L1 antibody (clone number: 28–8, Abcam, Cambridge, Massachusetts, United States).

Cytoplasmic and/or membranous positive intensity was graded as follows: very mild staining, mild staining, moderate staining, and intense staining using Image J, 1.41a (National Institutes of Health, United States) image analysis software. The mean area fraction of the stained cells was calculated by counting immunostained cells in three fields of each case by two pathologists. Data was entered in SPSS program for analysis.

Results PD-L1 was overexpressed on tumor cells of oral extranodal DLBCL than control cells from lesion free areas of oral tissues of the same patient.

Keywords

oral extranodal diffuse B cell lymphoma - diffuse large B cell lymphoma - programmed cell death ligand 1

Full Text

References

References
1 Silva TD, Ferreira CB, Leite GB, de Menezes Pontes JR, Antunes HS. Oral manifestations of lymphoma: a systematic review. Ecancermedicalscience 2016; 10: 665
2 Boussios S, Zerdes I, Vassou A. et al. Extranodal diffuse large B-cell lymphomas: a retrospective case series and review of the literature. Hematol Rep 2018; 10 (01) 7070
3 Møller MB, Pedersen NT, Christensen BE. Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal presentation–a population-based study of 1575 cases. Br J Haematol 2004; 124 (02) 151-159
4 Vitolo U, Seymour JF, Martelli M. et al; ESMO Guidelines Committee. Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27 (Suppl. 05) v91-v102
5 Iguchi H, Wada T, Matsushita N, Oishi M, Yamane H. Anatomic distribution of hematolymphoid malignancies in the head and neck: 7 years of experience with 122 patients in a single institution. Acta Otolaryngol 2012; 132 (11) 1224-1231
6 Bangash M, Hussain I, Zakaria M, Piracha M. Pattern of extranodal involvement in non-Hodgkin's lymphoma. Pak Armed Forces Med J 2014; 64 (04) 605-608
7 Hart S, Horsman JM, Radstone CR, Hancock H, Goepel JR, Hancock BW. Localised extranodal lymphoma of the head and neck: the Sheffield Lymphoma Group experience (1971-2000). Clin Oncol (R Coll Radiol) 2004; 16 (03) 186-192
8 Bagan JV, Carbonell F, Gómez MJ. et al. Extra-nodal B-cell non-Hodgkin's lymphomas of the head and neck: a study of 68 cases. Am J Otolaryngol 2015; 36 (01) 57-62
9 Gotoa M, Saitob M, Kuroyanagic N. et al. Intraosseous lymphoma of the oral and maxillofacial regions: report of our experiences, involving some difficult cases to be diagnosed, case report. J Oral Maxillofac Surg Med Pathol 2016; (28) 41-46
10 Zapater E, Bagán JV, Carbonell F, Basterra J. Malignant lymphoma of the head and neck. Oral Dis 2010; 16 (02) 119-128
11 Chi HS, Lee KW, Chiang FY. et al. Head and neck extranodal lymphoma in a single institute: a 17-year retrospective analysis. Kaohsiung J Med Sci 2012; 28 (08) 435-441
12 Roschewski M, Staudt LM, Wilson WH. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol 2014; 11 (01) 12-23
13 Liu J, Quan L, Zhang C, Liu A, Tong D, Wang J. Over-activated PD-1/PD-L1 axis facilitates the chemoresistance of diffuse large B-cell lymphoma cells to the CHOP regimen. Oncol Lett 2018; 15 (03) 3321-3328
14 Keane C, Gill D, Vari F, Cross D, Griffiths L, Gandhi M. CD4(+) tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy. Am J Hematol 2013; 88 (04) 273-276
15 Keane C, Vari F, Hertzberg M. et al. Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study. Lancet Haematol 2015; 2 (10) e445-e455
16 Kridel R, Steidl C, Gascoyne RD. Tumor-associated macrophages in diffuse large B-cell lymphoma. Haematologica 2015; 100 (02) 143-145
17 Bachy E, Coiffier B. Anti-PD1 antibody: a new approach to treatment of lymphomas. Lancet Oncol 2014; 15 (01) 7-8
18 Kim JR, Moon YJ, Kwon KS. et al. Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. PLoS One 2013; 8 (12) e82870
19 Zhao S, Zhang M, Zhanget Y. et al. The prognostic value of programmed cell death ligand 1 expression in non-Hodgkin lymphoma: a meta-analysis. Cancer Biol Med 2018; 15 (03) 290-298
20 Hu LY, Xu XL, Rao HL. et al. Expression and clinical value of programmed cell death-ligand 1 (PD-L1) in diffuse large B cell lymphoma: a retrospective study. Chin J Cancer 2017; 36 (01) 94
21 Gato-Cañas M, Zuazo M, Arasanz H. et al. PDL1 Signals through conserved sequence motifs to overcome interferon-mediated cytotoxicity. Cell Rep 2017; 20 (08) 1818-1829
22 Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26: 677-704
23 Westin JR, Chu F, Zhang M. et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol 2014; 15 (01) 69-77
24 Kiyasu J, Miyoshi H, Hirata A. 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) 2193-2201
25 Kaczmarek E, Górna A, Majewski P. Techniques of image analysis for quantitative immunohistochemistry. Rocz Akad Med Bialymst 2004; 49 (1, Suppl 1): 155-158
26 Ramanathan A, Mahmoud HA, Hui LP, Mei NY, Valliappan V, Zain RB. Oral extranodal non-Hodgkin's lymphoma: series of forty two cases in Malaysia. Asian Pac J Cancer Prev 2014; 15 (04) 1633-1637
27 van der Waal RI, Huijgens PC, van der Valk P, van der Waal I. Characteristics of 40 primary extranodal non-Hodgkin lymphomas of the oral cavity in perspective of the new WHO classification and the International Prognostic Index. Int J Oral Maxillofac Surg 2005; 34 (04) 391-395
28 Shah GH, Panwar SK, Chaturvedi PP, Kane SN. Isolated primary extranodal lymphoma of the oral cavity: A series of 15 cases and review of literature from a tertiary care cancer centre in India. Indian J Med Paediatr Oncol 2011; 32 (02) 76-81
29 Kemp S, Gallagher G, Kabani S, Noonan V, O'Hara C. Oral non-Hodgkin's lymphoma: review of the literature and World Health Organization classification with reference to 40 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 105 (02) 194-201
30 Takahashi H, Tezuka F, Fujita S, Okabe H. Primary extranodal non-Hodgkin's malignant lymphoma of the oral region: analysis of 11 autopsy cases. J Oral Pathol 1987; 16 (05) 241-250
31 Triantafillidou K, Dimitrakopoulos J, Iordanidis F, Gkagkalis A. Extranodal non-Hodgkin lymphomas of the oral cavity and maxillofacial region: a clinical study of 58 cases and review of the literature. J Oral Maxillofac Surg 2012; 70 (12) 2776-2785
32 Eisenbud L, Sciubba J, Mir R, Sachs SA. Oral presentations in non-Hodgkin's lymphoma: a review of thirty-one cases. Part II. Fourteen cases arising in bone. Oral Surg Oral Med Oral Pathol 1984; 57 (03) 272-280
33 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
34 Petroff MG, Chen L, Phillips TA, Hunt JS. B7 family molecules: novel immunomodulators at the maternal-fetal interface. Placenta 2002; 23 (Suppl A): S95-S101
35 Dong H, Strome SE, Salomao DR. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8 (08) 793-800
36 Azuma T, Yao S, Zhu G, Flies AS, Flies SJ, Chen L. B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood 2008; 111 (07) 3635-3643
37 Georgiou K, Chen L, Berglund M. et al. Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas. Blood 2016; 127 (24) 3026-3034
38 Nicolae A, Pittaluga S, Abdullah S. et al. EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood 2015; 126 (07) 863-872
39 Chen BJ, Chapuy B, Ouyang J. et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res 2013; 19 (13) 3462-3473
40 Fest T, Cerhan JR, Gandhi MK. et al. Validation of elevated blood soluble PD-L1 as an independent prognostic marker in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Blood 2014; 124: 2998