Cyclin D3 expression in non-hodgkin lymphoma : Correlation with other cell cycle regulators and clinical features

• Published in: American journal of clinical pathology 2001-03, Vol.115 (3), p.404-412
• Main Authors: MØLLER, Michael B, NIELSEN, Ole, PEDERSEN, Niels T
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Cycle Proteins; Cell Division; Cyclin D3; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclins - analysis; Disease-Free Survival; Female; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - chemistry; Lymphoma, B-Cell - pathology; Lymphoma, Non-Hodgkin - chemistry; Lymphoma, Non-Hodgkin - mortality; Lymphoma, Non-Hodgkin - pathology; Lymphoma, T-Cell - chemistry; Lymphoma, T-Cell - pathology; Male; Medical sciences; Microtubule-Associated Proteins - analysis; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Recurrence; Registries; Survival Rate; Tumor Suppressor Protein p53 - analysis; Tumor Suppressor Proteins
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1309/8KF0-0Y0C-2F4L-UHXL

Cyclin D3 is the most widely expressed D-type cyclin and can be rate limiting for G1/S transition. To study the expression of cyclin D3 in non-Hodgkin lymphoma, samples from 198 previously untreated patients with lymphoma from a prospectively collected, population-based lymphoma registry were analyzed immunohistochemically for cyclin D3 expression. In 43 lymphomas (21.7%), cyclin D3 was overexpressed. T-cell lymphomas more frequently overexpressed cyclin D3 than B-cell lymphomas. Furthermore, cyclin D3-overexpressing indolent lymphomas were associated with higher proliferation rate, higher p21Waf1 expression, lower p27Kip1 expression, and altered p53. Cyclin D3 overexpression identified a subgroup of patients with indolent B-cell lymphoma with adverse clinical features: patients were older, more frequently had "B" symptoms and extranodal involvement, and were more frequently in the high-intermediate or high-risk International Prognostic Index groups. At univariate analysis of indolent lymphomas, cyclin D3 overexpression was associated significantly with poor overall survival and poor relapse-free survival. The statistical significance was retained on multivariate analysis of overall survival and relapse-free survival. Our results suggest that cyclin D3 is expressed differentially among lymphoma subtypes and that overexpression might identify a subpopulation of patients with indolent lymphoma with adverse clinical features and poor outcome.