Cyclin D3 expression in non-Hodgkin lymphoma - Correlation with other cellcycle regulators and clinical features

Cyclin D3 is the most widely expressed D-type cyclin and can be rate limiti ng for G(1)/S transition. To study the expression of cyclin D3 in non-Hodgk in lymphoma, samples from 198 previously untreated patients with lymphoma f rom a prospectively collected, population-based lymphoma registry were anal yzed immunohistochemically for cyclin D3 expression. In 43 lymphomas (21.7% ), cyclin D3 was overexpressed. T-cell lymphomas more frequently overexpres sed cyclin D3 than B-cell lymphomas. Furthermore, cyclin D3-overexpressing indolent lymphomas were associated with higher proliferation rate, higher p 21(Waf1) expression, lower p27(Kip1) expression, and altered p53. Cyclin D3 overexpression identified a subgroup of patients with indolent B-cell lymp homa with adverse clinical features: patients were older more frequently ha d "B" symptoms and extranodal involvement, and were more frequently in the high-intermediate or highrisk International Prognostic Index groups. At uni variate analysis of indolent lymphomas, cyclin D3 overexpression was associ ated significantly with poor overall survival and poor relapse-free surviva l. The statistical significance was retained on multivariate analysis of ov erall survival and relapse-free survival. Our results suggest that cyclin D 3 is expressed differentially among lymphoma subtypes and that overexpressi on might identify a subpopulation of patients with indolent lymphoma with a dverse clinical features and poor outcome.