Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma

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-β), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P=0.025) or PKC-β (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-β 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-β was an independent predictor of poor overall survival (P=0.035). Cyclin D2 and PKC-β expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.