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Updated: Jul 30, 2026

Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
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.
Abstract:
Approximately 30% of multiple myelomas (MMs) express cyclin D1 when assessed using immunohistochemical techniques. Cyclin D1 expression correlates with greater tumor burden in MM, because cyclin D1-positive cases are more frequently associated with extensive bone marrow involvement, i.e., high pathologic stage, than are cyclin D1-negative cases. The mechanisms that explain this association are unknown. To explore other differences between cyclin D1-positive and cyclin D1-negative MMs, we assessed 59 MMs immunohistochemically for several G1 cell-cycle regulatory proteins, including cyclin D1, E2F-1, p53, mdm-2, and p21waf-1, using routinely fixed and processed, paraffin-embedded bone marrow specimens. Twenty MMs (34%) were cyclin D1 positive, and 39 (66%) were cyclin D1 negative. Eighteen (90%) of 20 cyclin D1-positive MMs were Stage III, in contrast to 19 (49%) of 39 cyclin D1-negative MMs (P = .003). Cyclin D1-positive MMs were more likely to express E2F-1 (16/20 vs. 4/39, P < .001), p53 (11/20 vs. 10/39, P = .041), and p21waf-1 (12/20 vs. 7/39, P = .003). There was no significant difference in mdm-2 expression between these groups. We also assessed proliferation rate using an antibody specific for the Ki-67 antigen. A relatively high percentage (> 20%) of Ki-67-positive cells was found in cyclin D1-positive MMs compared with cyclin D1-negative MMs (13/20 vs. 3/39, P < 0.001). These results suggest that cyclin D1-positive MMs are more likely to possess additional derangements involving other G1 cell-cycle regulatory proteins. We speculate that these abnormalities might result in increased proliferation, thereby explaining the correlation between cyclin D1 expression and greater tumor burden.
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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