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Open Access 01-12-2021 | Lymphoma | Research

Application of CD54 in diagnosing bone marrow involvement by using flow cytometry in patients with diffuse large B-cell lymphoma

Authors: Wei Wang, Yan Li, Xavier Rivera Rivera, Linjun Zhao, Di Mei, Wenqing Hu, Bin Jiang

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Flow cytometry plays a key role in detecting bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL). To improve its detection sensitivity, we need to explore novel markers. In this study, we detected the expression CD54 on lymphoma cells in BM specimens from DLBCL patients and clarified its diagnostic significance in BM involvement by DLBCL.

Methods

We collected BM specimens from 76 patients with DLBCL (germinal center B-cell (GCB) = 25, non-GCB = 51) and 10 control patients without lymphoma. We detected and compared the expression of CD54 on lymphoma cells and normal mature B cells by using 10-color panels.

Results

Normal plasma cells expressed a higher level of CD54 as compared with hematogones (p < 0.05) and normal mature B cells (p < 0.05). Among 76 patients, 23 of them (GCB = 12, non-GCB = 11) had BM involvement. Lymphoma B cells from 12 cases (GBC = 4, non-GCB = 8) expressed a higher level of CD54 compared to normal mature B cells (p < 0.05). Additionally, lymphoma cells of the non-GCB subtype frequently expressed a higher level of CD54 in comparison to the GCB subtype (p < 0.05). And the high expression of CD54 was not related to plasmacytoid differentiation.

Conclusion

Aberrant expression of CD54 on lymphoma cells is frequently seen in patients’ BM specimens involved by DLBCL, especially in the non-GCB subtype. CD54 could be used as a new marker to gate on lymphoma cells and improve the detection sensitivity of BM involvement in patients with DLBCL.

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Campbell J, Seymour JF, Matthews J, Wolf M, Stone J, Juneja S. The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement. Eur J Haematol. 2006;76(6):473–80. https://doi.org/10.1111/j.1600-0609.2006.00644.x.CrossRef

Chung R, Lai R, Wei P, Lee J, Hanson J, Belch AR, et al. Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the international prognostic index. Blood. 2007;110(4):1278–82. https://doi.org/10.1182/blood-2007-01-070300.CrossRef

Hodges GF, Lenhardt TM, Cotelingam JD. Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease. Am J Clin Pathol. 1994;101(3):305–11. https://doi.org/10.1093/ajcp/101.3.305.CrossRef

Duggan PR, Easton D, Luider J, Auer IA. Bone marrow staging of patients with non-Hodgkin lymphoma by flow cytometry: correlation with morphology. Cancer. 2000;88(4):894–9. https://doi.org/10.1002/(SICI)1097-0142(20000215)88:4<894::AID-CNCR21>3.0.CO;2-O.CrossRef

Greenbaum U, Levi I, Madmoni O, Lior Y, Al-Athamen K, Perry ZH, et al. The prognostic significance of bone marrow involvement in diffuse large B cell lymphoma according to the flow cytometry. Leuk Lymphoma. 2019;60(10):2477–82. https://doi.org/10.1080/10428194.2019.1587755.CrossRef

Kim B, Lee ST, Kim HJ, Kim SH. Bone marrow flow cytometry in staging of patients with B-cell non-Hodgkin lymphoma. Ann Lab Med. 2015;35(2):187–93. https://doi.org/10.3343/alm.2015.35.2.187.CrossRef

Morice WG, Kurtin PJ, Hodnefield JM, Shanafelt TD, Hoyer JD, Remstein ED, et al. Predictive value of blood and bone marrow flow cytometry in B-cell lymphoma classification: comparative analysis of flow cytometry and tissue biopsy in 252 patients. Mayo Clin Proc. 2008;83(7):776–85. https://doi.org/10.4065/83.7.776.CrossRef

Perea G, Altes A, Bellido M, Aventin A, Bordes R, Ayats R, et al. Clinical utility of bone marrow flow cytometry in B-cell non-Hodgkin lymphomas (B-NHL). Histopathology. 2004;45(3):268–74. https://doi.org/10.1111/j.1365-2559.2004.01937.x.CrossRef

Seegmiller AC, Hsi ED, Craig FE. The current role of clinical flow cytometry in the evaluation of mature B-cell neoplasms. Cytometry B Clin Cytom. 2019;96:20–9 https://doi.org/10.1002/cyto.b.21756.PubMed

10.

Onciu M, Berrak SG, Medeiros LJ, Katz RL, Huh YO. Discrepancies in the immunophenotype of lymphoma cells in samples obtained simultaneously from different anatomic sites. Am J Clin Pathol. 2002;117(4):644–50. https://doi.org/10.1309/urtd-7md9-u8n1-c60q.CrossRef

11.

van de Stolpe A, van der Saag PT. Intercellular adhesion molecule-1. J Mol Med (Berl). 1996;74(1):13–33. https://doi.org/10.1007/BF00202069.CrossRef

12.

Kuhlman P, Moy VT, Lollo BA, Brian AA. The accessory function of murine intercellular adhesion molecule-1 in T lymphocyte activation. Contributions of adhesion and co-activation. J Immunol. 1991;146:1773–82.PubMed

13.

Boyd AW, Wawryk SO, Burns GF, Fecondo JV. Intercellular adhesion molecule 1 (ICAM-1) has a central role in cell-cell contact-mediated immune mechanisms. Proc Natl Acad Sci U S A. 1988;85(9):3095–9. https://doi.org/10.1073/pnas.85.9.3095.CrossRefPubMedPubMedCentral

14.

Gregory CD, Murray RJ, Edwards CF, Rickinson AB. Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt’s lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med. 1988;167(6):1811–24. https://doi.org/10.1084/jem.167.6.1811.CrossRefPubMed

15.

Gascoyne RD CE, Jaffe ES, Chan WC, Chan JKC, Rosenwald A, Stein H, et al. Diffuse large B-cell lymphoma, NOS. In: Swerdlow SH CE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, et al, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2017: 291–297.

16.

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. https://doi.org/10.1182/blood-2016-01-643569.CrossRef

17.

Shim H, Oh JI, Park SH, Jang S, Park CJ, Huh J, et al. Prognostic impact of concordant and discordant cytomorphology of bone marrow involvement in patients with diffuse, large, B-cell lymphoma treated with R-CHOP. J Clin Pathol. 2013;66(5):420–5. https://doi.org/10.1136/jclinpath-2012-201158.CrossRef

18.

Campbell JK, Matthews JP, Seymour JF, Wolf MM, Juneja SK. Australasian Leukaemia Lymphoma G. Optimum trephine length in the assessment of bone marrow involvement in patients with diffuse large cell lymphoma. Ann Oncol. 2003;14:273–6 https://doi.org/10.1093/annonc/mdg055.CrossRef

19.

Chantepie SP, Cornet E, Salaun V, Reman O. Hematogones: an overview. Leuk Res. 2013;37(11):1404–11. https://doi.org/10.1016/j.leukres.2013.07.02.CrossRef

20.

Boy S, van Heerden M, Pool R, Willem P, Slavik T. Plasmablastic lymphoma versus diffuse large B cell lymphoma with plasmablastic differentiation: proposal for a novel diagnostic scoring system. J Hematop. 2015;8(1):10. https://doi.org/10.1007/s12308-014-0227-y–1.CrossRef

21.

Jourdan M, Caraux A, Caron G, Robert N, Fiol G, Reme T, et al. characterization of a transitional preplasmablast population in the process of human B cell to plasma cell differentiation. J Immunol. 2011;187(8):3931–41. https://doi.org/10.4049/jimmunol.1101230.CrossRef

22.

Ohmoto A, Maeshima AM, Taniguchi H, Tanioka K, Makita S, Kitahara H, et al. Histopathological analysis of B-cell non-Hodgkin lymphomas without light chain restriction by using flow cytometry. Leuk Lymphoma. 2015;56(12):3301–5. https://doi.org/10.3109/10428194.2015.1034702.CrossRef

23.

Tomita N, Takeuchi K, Hyo R, Hashimoto C, Takemura S, Taguchi J, et al. Diffuse large B cell lymphoma without immunoglobulin light chain restriction by flow cytometry. Acta Haematol. 2009;121(4):196–201. https://doi.org/10.1159/000220332.CrossRef

24.

Brudno J, Tadmor T, Pittaluga S, Nicolae A, Polliack A, Dunleavy K. Discordant bone marrow involvement in non-Hodgkin lymphoma. Blood. 2016;127(8):965–70. https://doi.org/10.1182/blood-2015-06-651968.CrossRef

25.

Ozkaya N, Bassullu N, Demiroz AS, Tuzuner N. Discrepancies in Lymphoma Diagnosis Over the Years: A 13-Year Experience in a Tertiary Center. Turk J Haematol. 2017;34:81–8 https://doi.org/10.4274/tjh.2016.0344.CrossRef

26.

Shanafelt TD, Ghia P, Lanasa MC, Landgren O, Rawstron AC. Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management. Leukemia. 2010;24(3):512–20. https://doi.org/10.1038/leu.2009.287.CrossRef

27.

Pillai RK, Surti U, Swerdlow SH. Follicular lymphoma-like B cells of uncertain significance (in situ follicular lymphoma) may infrequently progress, but precedes follicular lymphoma, is associated with other overt lymphomas and mimics follicular lymphoma in flow cytometric studies. Haematologica. 2013;98(10):1571–80. https://doi.org/10.3324/haematol.2013.085506.CrossRef

28.

Kussick SJ, Kalnoski M, Braziel RM, Wood BL. Prominent clonal B-cell populations identified by flow cytometry in histologically reactive lymphoid proliferations. Am J Clin Pathol. 2004;121(4):464–72. https://doi.org/10.1309/4EJ8-T3R2-ERKQ-61WH. https://doi.org/10.1309/4EJ8T3R2ERKQ61WH.CrossRefPubMed

29.

Cherian S, Wood B. Flow Cytometry in evaluation of hematopoietic neoplasms: a case-based approach. Northfield: College of American Pathologists. 2012;14.

30.

Luo RF, Zhao S, Tibshirani R, Myklebust JH, Sanyal M, Fernandez R, et al. CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas. Hum Pathol. 2010;41:271–80. https://doi.org. https://doi.org/10.1016/j.humpath.2009.07.022.CrossRefPubMed

31.

Cardoso CC, Auat M, Santos-Pirath IM, Rudolf-Oliveira RCM, da Silva JP, Lange BG, et al. The importance of CD39, CD43, CD81, and CD95 expression for differentiating B cell lymphoma by flow cytometry. Cytometry B Clin Cytom. 2018;94(3):451–8. https://doi.org/10.1002/cyto.b.21533.CrossRef

32.

Terol MJ, Lopez-Guillermo A, Bosch F, Villamor N, Cid MC, Rozman C, et al. Expression of the adhesion molecule ICAM-1 in non-Hodgkin's lymphoma: relationship with tumor dissemination and prognostic importance. J Clin Oncol. 1998;16(1):35–40. https://doi.org/10.1200/JCO.1998.16.1.35.CrossRef

33.

Stopeck AT, Gessner A, Miller TP, Hersh EM, Johnson CS, Cui H, et al. Loss of B7.2 (CD86) and intracellular adhesion molecule 1 (CD54) expression is associated with decreased tumor-infiltrating T lymphocytes in diffuse B-cell large-cell lymphoma. Clin Cancer Res. 2000;6:3904–9.PubMed

34.

Schniederjan SD, Li S, Saxe DF, Lechowicz MJ, Lee KL, Terry PD, et al. A novel flow cytometric antibody panel for distinguishing Burkitt lymphoma from CD10+ diffuse large B-cell lymphoma. Am J Clin Pathol. 2010;133:718–26 https://doi.org/10.1309/AJCP0XQDGKFR0HTW.CrossRef

35.

Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121(4):482–8. https://doi.org/10.1309/74R4-TB90-BUWH-27JX. https://doi.org/10.1309/74R4TB90BUWH27JX.CrossRefPubMed

36.

Reid S, Yang S, Brown R, Kabani K, Aklilu E, Ho PJ, et al. Characterisation and relevance of CD138-negative plasma cells in plasma cell myeloma. Int J Lab Hematol. 2010;32(6p1):e190–6. https://doi.org/10.1111/j.1751-553X.2010.01222.x.CrossRef

Title: Application of CD54 in diagnosing bone marrow involvement by using flow cytometry in patients with diffuse large B-cell lymphoma
Authors: Wei Wang
Yan Li
Xavier Rivera Rivera
Linjun Zhao
Di Mei
Wenqing Hu
Bin Jiang
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Lymphoma
Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08753-0

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