Expression of Adhesion Molecule CD56 in Tumor Plasma Cells in Bone Marrow as a Prognostic Factor in Multiple Myeloma

LYMPHOID TUMORS , , , ,

MV Firsova, LP Mendeleeva, AM Kovrigina, MV Solov’ev, NL Deineko, MYu Drokov, VG Savchenko

National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Maiya Valer’evna Firsova, MD, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: firs-maia@yandex.ru

For citation: Firsova MV, Mendeleeva LP, Kovrigina AM, et al. Expression of Adhesion Molecule CD56 in Tumor Plasma Cells in Bone Marrow as a Prognostic Factor in Multiple Myeloma. Clinical oncohematology. 2019;12(4):377–84 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-377-384

ABSTRACT

Aim. To study immunohistochemical parameters of tumor plasma cells in bone marrow and to assess how the expression of adhesion molecule CD56 impacts overall survival (OS) of multiple myeloma (MM) patients.

Materials & Methods. The trial included 35 patients (19 men and 16 women) aged 23 to 73 years (with median age of 58 years) with newly diagnosed MM. At disease onset plasmacytoma was diagnosed in 21 patients. In all patients bone marrow core biopsy was performed followed by histologic and immunohistochemical (IHC) examinations. IHC examination was based on the panel of CD56, CD166, CXCR4, Ki-67, and c-MYC/CD138 antibodies. Kaplan-Meier survival curves and significance assessment by means of Cox’s F-Test were used.

Results. Expression mean values of most of studied markers (CD56, CXCR4, c-MYC, and Ki-67) in bone marrow of patients without plasmacytoma (n = 14) appeared to be higher than in patients with plasmacytoma at MM onset. Expression mean value is understood as percentage ratio of plasma cells expressing a studied marker to total cell count of tumor substrate. High expression of chemokine receptors (CXCR4), and adhesion molecules (CD56) probably inhibits plasma cell migration and impedes extramedullary tumor progression. Comparison of protein expression by tumor plasma cells in bone marrow in the groups with bone extramedullary plasmacytoma shows a distinct regularity referring to CD56 adhesion molecule. For example, CD56 expression is significantly (p < 0.05) lower in terms of the count of tumor plasma cells with marker expression in bone marrow of MM patients with extramedullary plasmacytoma compared with patients with bone plasmacytoma (1 ± 1 % vs. 65.71 ± 12.12 %). Comparison of MM patients’ OS depending on CD56 expression by tumor plasma cells in bone marrow showed that 4-year OS of patients with CD56 expression in bone marrow was significantly higher being 80 % vs. 38 % in the group with CD56 expression less than in 10 % of tumor cells.

Conclusion. Expression of adhesion molecule CD56 in tumor plasma cells in bone marrow can be regarded as a prognostic factor in MM. Probably, when at disease onset CD56 expression is identified in less than 10 % of tumor cells in bone marrow, more detailed additional examination of patients should be carried out to rule out extramedullary lesions in different organs and tissues.

Keywords: multiple myeloma, bone plasmacytoma, extramedullary plasmacytoma, bone marrow core biopsy, CD56.

Received: May 12, 2019

Accepted: September 2, 2019

Read in PDF

REFERENCES

  1. Фрейдлин И.С. Система мононуклеарных фагоцитов. М.: Медицина, 1984. 272 c.

    [Freidlin IS. Sistema mononuklearnykh fagotsitov. (The system of mononuclear phagocytes.) Moscow: Meditsina Publ.; 1984. 272 p. (In Russ)]

  2. Van Furth R, Raeburn JA, van Zwet TL. Characteristics of human mononuclear phagocytes. Blood. 1979;54(2):485–500.

  3. Mitsiades CS, McMillin DW, Klippel S, et al. The role of the bone marrow microenvironment in the pathophysiology of myeloma and its significance in the development of more effective therapies. Hematol Oncol Clin N Am. 2007;21(6):1007–34. doi: 10.1016/j.hoc.2007.08.007.

  4. Van Camp B, Durie BG, Spier C, et al. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). Blood. 1990;76(2):377–82.

  5. Sahara N, Takeshita A, Shigeno K, et al. Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma. Br J Haematol. 2002;117(4):882–5. doi: 10.1046/j.1365-2141.2002.03513.x.

  6. Cayrol R, Wosik K, Berard JL, et al. Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol. 2008;9(2):137–45. doi: 10.1038/ni1551.

  7. Masedunskas A, King JA, Tan F, et al. Activated leukocyte cell adhesion molecule is a component of the endothelial junction involved in transendothelial monocyte migration. FEBS Lett. 2006;580(11):2637–45. doi: 10.1016/j.febslet.2006.04.013.

  8. Avet-Loiseau H, Gerson F, Magrangeas F, et al. Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors. Blood. 2001;98(10):3082–6. doi: 10.1182/blood.v98.10.3082.

  9. Gabrea A, Martelli ML, Qi Y, et al. Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors. Genes Chromos Cancer. 2008;47(7):573–90. doi: 10.1002/gcc.20563.

  10. Gerdes J. Ki-67 and other proliferation markers useful for immunohistological diagnostic and prognostic evaluations in human malignancies. Semin Cancer Biol. 1990;1(3):199–206.

  11. Endl E, Steinbach P, Knuchel R, et al. Analysis of cell cycle-related Ki-67 and p120 expression by flow cytometric BrdUrd-Hoechst/7AAD and immunolabeling technique. Cytometry. 1997;29(3):233–41. doi: 10.1002/(sici)1097-0320(19971101)29:3<233::aid-cyto6>3.3.co;2-3.

  12. Kausch I, Lingnau A, Endl E, et al. Antisense treatment against Ki-67 mRNA inhibits proliferation and tumor growth in vitro and in vivo. Int J Cancer. 2003;105(5):710–6. doi: 10.1002/ijc.11111.

  13. Greipp PR, Lust JA, O’Fallon WM, et al. Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. Blood. 1993;81(12):3382–7.

  14. Tsirakis G, Pappa CA, Spanoudakis M, et al. Clinical significance of sCD105 in angiogenesis and disease activity in multiple myeloma. Eur J Intern Med. 2012;23(4):368–73. doi: 10.1016/j.ejim.2012.01.012.

  15. Tsirakis G, Pappa CA, Psarakis FE, et al. Serum concentrations and clinical significance of soluble CD40 ligand in patients with multiple myeloma. Med Oncol. 2012;29(4):2396–401. doi: 10.1007/s12032-012-0203-2.

  16. Tsirakis G, Pappa CA, Kaparou M, et al. The relationship between soluble receptor of interleukin-6 with angiogenic cytokines and proliferation markers in multiple myeloma. Tumour Biol. 2013;34(2):859–64. doi: 10.1007/s13277-012-0618-6.

  17. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000;18(1):217–42. doi: 10.1146/annurev.immunol.18.1.217.

  18. Oberlin E, Amara A, Bachelerie F, et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996;382(6594):833–5. doi: 10.1038/382833a0.

  19. Piazza R, Valletta S, Winkelmann N, et al. Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet. 2013;45(1):18–24. doi: 10.1038/ng.2495.

  20. Blade J, Fernandez de Larrea C, Rosinol L, et al. Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol. 2011;29(28):3805–12. doi: 10.1200/JCO.2011.34.9290.

  21. Usmani SZ, Heuck C, Mitchell A, et al. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012;97(11):1761–7. doi: 10.3324/haematol.2012.065698.

  22. Varettoni M, Corso A, Pica G, et al. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol. 2009;21(2):325–30. doi: 10.1093/annonc/mdp329.

  23. Weinstock M, Aljawai Y, Morgan EA, et al. Incidence and clinical features of extramedullary multiple myeloma in patients who underwent stem cell transplantation. Br J Haematol. 2015;169(6):851–8. doi: 10.1111/bjh.13383.

  24. Bao L, Lai Y, Liu Y, et al. CXCR4 is a good survival prognostic indicator in multiple myeloma patients. Leuk Res. 2013;37(9):1083–8. doi: 10.1016/j.leukres.2013.06.002.

  25. Xu L, Mohammad KS, Wu H, et al. Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma. Cancer Res. 2016;76(23):6901–10. doi: 10.1158/0008-5472.CAN-16-0517.