title: Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma.
abstract: We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-beta), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P = 0.025) or PKC-beta (P = 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-beta had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P = 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-beta was an independent predictor of poor overall survival (P = 0.035). Cyclin D2 and PKC-beta expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA. chans@unmc.edu
authors.forename: Christine P
authors.initials: CP
authors.lastname: Hans
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Patricia
authors.initials: P
authors.lastname: Aoun
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Cochran
authors.forename: Zenggang
authors.initials: Z
authors.lastname: Pan
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.forename: James C
authors.initials: JC
authors.lastname: Lynch
authors.forename: Robert Gregory
authors.initials: RG
authors.lastname: Bociek
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bierman
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000401:mortality*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011493:Protein Kinase C / Q000096:biosynthesis*; D064546:Protein Kinase C beta; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D011493:Protein Kinase C; D064546:Protein Kinase C beta