Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients

  • G. Tsirakis University Hospital of Heraklion, Greece.
  • C. A. Pappa Venizelion Hospital of Heraklion, Greece.
  • M. Kaparou University Hospital of Heraklion, Greece.
  • V. Katsomitrou University Hospital of Heraklion, Greece.
  • A. Hatzivasili Venizelion Hospital of Heraklion, Greece.
  • T. Alegakis University of Crete, Greece.
  • A. Xekalou University Hospital of Heraklion, Greece.
  • E. N. Stathopoulos University Hospital of Heraklion, Greece.
  • M. Alexandrakis | alexandm@med.uoc.gr University Hospital of Heraklion, Greece.

Abstract

Multiple myeloma (MM) is a malignant plasma cell disease. Several proinflammatory cytokines produced by malignant plasma cells and bone marrow (BM) stromal cells are involved in the pathogenesis of the disease. We evaluated serum levels of the proinflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), in MM patients before treatment, and determined its significance in tumor progression. We also analyzed the correlation between measured parameters with proliferating cell nuclear antigen (PCNA). Forty-four MM patients and 20 healthy controls were studied. Serum levels of the proinflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA), whereas PCNA value in the BM was determined by immunohistochemistry staining. The mean concentrations of the measured cytokines were significantly different among the three stages of disease, with higher values in advanced disease stage. Furthermore, patients with MM had significantly higher serum levels of the measured cytokines than in controls. A positive correlation was found between IL-6 with IL-1β, IL-8 and MIP-1α. Similarly, IL-8 and MIP-1α were positively correlated with markers of disease activity such as beta 2 microglobulin and LDH. The proliferation index, determined by PCNA immunostaining, was higher in advanced disease stage. Furthermore PCNA value correlated significantly with beta 2 microglobulin, LDH and the levels of the measured cytokines. Our results showed that the proliferative activity, as measured with PCNA, increases in parallel with disease stage. The positive correlation between PCNA and other measured mediators supports the involvement of these factors in the biology of myeloma cell growth and can be used as markers of disease activity and as possible therapeutic targets.

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Author Biographies

G. Tsirakis, University Hospital of Heraklion
Department of Hematology
C. A. Pappa, Venizelion Hospital of Heraklion
Department of Hematology
M. Kaparou, University Hospital of Heraklion
Department of Hematology
V. Katsomitrou, University Hospital of Heraklion
Department of Hematology
A. Hatzivasili, Venizelion Hospital of Heraklion
Department of Hematology
T. Alegakis, University of Crete
Department of Social Medicine
A. Xekalou, University Hospital of Heraklion
Department of Pathology
E. N. Stathopoulos, University Hospital of Heraklion
Department of Pathology
M. Alexandrakis, University Hospital of Heraklion
Department of Hematology
Published
2011-08-01
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Issue
Section
Brief Reports
Keywords:
Multiple myeloma, Interleukin-6, Interleukin-8, Interleukin-1β, MIP-1α, proliferating cell nuclear antigen
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How to Cite
Tsirakis, G., Pappa, C. A., Kaparou, M., Katsomitrou, V., Hatzivasili, A., Alegakis, T., Xekalou, A., Stathopoulos, E. N., & Alexandrakis, M. (2011). Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients. European Journal of Histochemistry, 55(3), e21. https://doi.org/10.4081/ejh.2011.e21