Prognostic impact of protein kinase C β II expression in R-CHOP-treated diffuse large B-cell lymphoma patients

Abstract

Development of targeted agents for the treatment of diffuse large B-cell lymphoma includes clinical evaluation of enzastaurin, an agent that suppresses signaling through protein kinase C-β and AKT pathways. To determine whether protein kinase C-β expression has prognostic significance for diffuse large B-cell lymphoma patients treated with immunochemotherapy, we analyzed the expression of protein kinase C-β II, BCL-2 and cell of origin immunohistochemically from pretreatment samples of 95 diffuse large B-cell lymphoma patients. All patients received rituximab with CHOP or CHOEP. According to Kaplan–Meier analyses, overall survival at 3 years was better among the patients with low than high protein kinase C-β II protein levels (94 vs 76%, P=0.036). The prognostic value of protein kinase C-β II expression on survival was seen in the patients with low and high International Prognostic Index risk groups, and in all molecular entities. Gene expression data from an independent set of 233 diffuse large B-cell lymphoma patients treated with a combination of rituximab and CHOP-like chemotherapy was analyzed in comparison. Accordingly, a better 3-year overall survival was observed among the subgroup with low protein kinase C-β II mRNA levels (84 vs 68%, P=0.005). In multivariate analysis with cell of origin, protein kinase C-β II mRNA expression remained as an independent predictor for overall survival. Together, the data show that protein kinase C-β II expression has prognostic significance in diffuse large B-cell lymphoma patients treated with immunochemotherapy.