Cyclin D3 is an important regulator for transition from G(1) to the S phase of the cell cycle.
Cyclin D3 expression is associated with cell proliferation in lymphoid tissues, but its impact on clinical outcome in non-Hodgkin's
lymphomas has not been studied. Therefore, we determined the clinical relevance of
cyclin D3 expression in patients with
diffuse large B-cell lymphoma. We examined the relation between
cyclin D3 expression at diagnosis and response to conventional
polychemotherapy and overall survival in 81 previously untreated patients with
diffuse large B-cell lymphoma.
Cyclin D3 expression was assessed by immunohistochemistry.
Cyclin D3 immunostaining ranged from 0-100% (median, 30%) of the
lymphoma cells. Patients with high (>or=50%
cyclin D3-positive
lymphoma cells)
cyclin D3 expression had a more advanced clinical stage (P = 0.003) and more often had extranodal disease in more than one site (P = 0.007) than patients with low
cyclin D3 expression. Patients with high
cyclin D3 expression had a significantly lower complete response rate (17% versus 74%; P < 0.001) and a shorter overall survival (3-year survival rate, 18% versus 74%; P < 0.001) than those with low
cyclin D3 expression. Multivariate analyses that included
cyclin D3 and the International Prognostic Index demonstrated that
cyclin D3 expression had independent effects on the complete response rates and overall survival of the patients. In conclusion, high
cyclin D3 expression is an independent predictive and prognostic factor associated with poor clinical outcome in patients with
diffuse large B-cell lymphoma.