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Cyclin D1 expression in peripheral T-cell lymphomas
Joo Y Song1, Liping Song1, Alex F Herrera2
1Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
Summary
Cyclin D1 overexpression, typically seen in B-cell lymphomas, is also found in some T-cell lymphomas, particularly ALK+ anaplastic large cell lymphoma. This finding suggests cyclin D1 may be a therapeutic target in T-cell lymphomas.
Area of Science:
- Oncology
- Cell Biology
- Hematopathology
Background:
- Cyclin D1 is a key cell cycle regulator, frequently overexpressed in B-cell neoplasms like mantle cell lymphoma.
- Expression patterns of cyclin D1 in T-cell lymphomas are not well-characterized.
- Targeting cyclin-dependent kinase pathways is a focus for novel cancer therapies.
Purpose of the Study:
- To investigate the expression of cyclin D1 in a diverse cohort of peripheral T-cell lymphomas.
- To determine if cyclin D1 overexpression in T-cell lymphomas could represent a therapeutic target.
- To correlate cyclin D1 expression with genetic alterations (IGH/CCND1 translocation or gene amplification).
Main Methods:
- Immunohistochemistry for cyclin D1 protein (SP4 clone) on 200 paraffin-embedded peripheral T-cell lymphoma tissues.
- Fluorescence in situ hybridization (FISH) for IGH/CCND1 translocation and CCND1 gene amplification in a subset of cases.
- Classification of T-cell lymphomas included ALK+ ALCL, ALK- ALCL, PTCL-NOS, AITL, ENKTCL, EATL, HSTCL, CTCL, and LGLL.
Main Results:
- Cyclin D1 overexpression was detected in 8/34 (24%) ALK+ ALCL and 3/44 (7%) ALK- ALCL cases.
- Three cases (4%) of PTCL-NOS also showed cyclin D1 positivity.
- All other T-cell lymphoma subtypes were negative for cyclin D1. FISH analysis was negative for IGH/CCND1 translocation or extra copies in positive cases.
Conclusions:
- Cyclin D1 overexpression is not exclusive to B-cell lymphomas and occurs in a subset of peripheral T-cell lymphomas, notably ALK+ anaplastic large cell lymphoma.
- The observed cyclin D1 overexpression in T-cell lymphomas may result from post-translational modifications rather than genetic alterations.
- Cyclin D1 represents a potential therapeutic target in specific T-cell lymphomas, particularly ALK+ ALCL, for which cyclin-dependent kinase pathway inhibitors could be beneficial.
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