Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle regulators and clinical features.
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.
Department of Pathology, Odense University Hospital, Winsløwparken 15, DK-5000 Odense C, Denmark.
M B
MB
Møller
O
O
Nielsen
N T
NT
Pedersen
D018797:Cell Cycle Proteins; D002455:Cell Division; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000737:chemistry / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins
C534696:CCND3 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27