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Bcl-1/cyclin D1 in malignant lymphoma
C J de Boer1, J H van Krieken, E Schuuring
1Department of Pathology, Leiden University Hospital, The Netherlands.
Summary
Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma. The cyclin D1 gene overexpression, often due to the t(11;14) translocation, is a key diagnostic marker for MCL.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma (NHL) representing 2%-10% of cases.
- MCL typically presents as generalized disease with a poor prognosis.
- Distinct histologic and cytologic patterns exist, but the immunophenotype is consistent, notably expressing cyclin D1.
Purpose of the Study:
- To investigate the diagnostic utility of cyclin D1 expression and the t(11;14) translocation in mantle cell lymphoma.
- To explore additional genetic abnormalities associated with MCL progression.
Main Methods:
- Immunohistochemistry for cyclin D1 expression.
- Cytogenetic analysis including PCR, Southern blot, and fluorescence in situ hybridization (FISH) for the t(11;14) translocation.
- DNA fiber FISH for breakpoint mapping and analysis of other genetic abnormalities (p53, p16).
Main Results:
- The t(11;14) translocation is detected in 35%-66% of MCL cases by conventional methods, but FISH suggests nearly all cyclin D1-expressing MCLs harbor this translocation.
- Cyclin D1 gene overexpression occurs at the RNA level in approximately 90% of MCLs.
- Immunohistochemistry for cyclin D1 is a highly effective diagnostic marker for MCL, with expression being low or undetectable in normal lymphoid cells and other B-cell lymphomas.
Conclusions:
- Cyclin D1 overexpression, driven by the t(11;14) translocation, is a hallmark of mantle cell lymphoma.
- Advanced techniques like FISH improve the detection rate of the t(11;14) translocation.
- Immunohistochemistry for cyclin D1 is a reliable and valuable diagnostic tool for identifying MCL.