Expression of the cell-cycle-related proteins E2F-1, p53, mdm-2, p21waf-1, and Ki-67 in multiple myeloma: correlation

R Lai1, L J Medeiros, C S Wilson

  • 1Division of Pathology, City of Hope National Medical Center, Duarte, California, USA.

Insights

Multiple myeloma (MM) cases expressing cyclin D1 show higher tumor burden and advanced stage. Cyclin D1-positive MM also exhibits increased expression of cell-cycle regulators and higher proliferation rates.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • Multiple myeloma (MM) is a cancer of plasma cells.
  • Approximately 30% of MM cases express cyclin D1.
  • Cyclin D1 expression in MM correlates with increased tumor burden and advanced pathologic stage, but the underlying mechanisms are unclear.

Purpose of the Study:

  • To investigate differences in cell-cycle regulatory protein expression and proliferation rates between cyclin D1-positive and cyclin D1-negative MM.
  • To explore potential mechanisms linking cyclin D1 expression to greater tumor burden in MM.

Main Methods:

  • Immunohistochemical analysis of 59 MM bone marrow specimens.
  • Assessment of G1 cell-cycle regulatory proteins: cyclin D1, E2F-1, p53, mdm-2, and p21waf-1.
  • Evaluation of proliferation rate using Ki-67 antigen staining.

Main Results:

  • Cyclin D1-positive MM (34% of cases) were significantly more likely to be Stage III compared to cyclin D1-negative MM (P = .003).
  • Cyclin D1-positive MM showed higher expression of E2F-1 (P < .001), p53 (P = .041), and p21waf-1 (P = .003).
  • A higher proliferation rate (Ki-67 positive cells >20%) was observed in cyclin D1-positive MM (P < 0.001).

Conclusions:

  • Cyclin D1-positive MM cases frequently exhibit additional alterations in G1 cell-cycle regulatory proteins.
  • These molecular abnormalities may contribute to increased proliferation in cyclin D1-positive MM.
  • The findings suggest a potential mechanism for the association between cyclin D1 expression and greater tumor burden in multiple myeloma.

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