title: Cyclin D3 is a predictive and prognostic factor in diffuse large B-cell lymphoma.
abstract: 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.
authors.affiliation: Department of Internal Medicine I, Division of Oncology, University of Vienna, A-1090 Vienna, Austria. martin.filipits@akh-wien.ac.at
authors.forename: Martin
authors.initials: M
authors.lastname: Filipits
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaeger
authors.forename: Gudrun
authors.initials: G
authors.lastname: Pohl
authors.forename: Thomas
authors.initials: T
authors.lastname: Stranzl
authors.forename: Ingrid
authors.initials: I
authors.lastname: Simonitsch
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Cathrin
authors.initials: C
authors.lastname: Skrabs
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002453:Cell Cycle; D002455:Cell Division; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins