Prognostic impact of protein kinase C beta 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-beta and AKT pathways. To determine whether protein kinase C-beta expression has prognostic significance for diffuse large B-cell lymphoma patients treated with immunochemotherapy, we analyzed the expression of protein kinase C-beta 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-beta II protein levels (94 vs 76%, P=0.036). The prognostic value of protein kinase C-beta 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-beta II mRNA levels (84 vs 68%, P=0.005). In multivariate analysis with cell of origin, protein kinase C-beta II mRNA expression remained as an independent predictor for overall survival. Together, the data show that protein kinase C-beta II expression has prognostic significance in diffuse large B-cell lymphoma patients treated with immunochemotherapy.

• Authors: Sari Riihijärvi, Satu Koivula, Heidi Nyman, Karin Rydström, Mats Jerkeman, Sirpa Leppä
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 23 Issue 5 Pg. 686-93 (May 2010) ISSN: 1530-0285 [Electronic] United States
• PMID: 20190733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vincristine
• Doxorubicin
• Cyclophosphamide
• Protein Kinase C
• Protein Kinase C beta
• Prednisone

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chi-Square Distribution
• Cyclophosphamide (therapeutic use)
• Doxorubicin (therapeutic use)
• Female
• Humans
• Immunohistochemistry
• Lymphoma, Large B-Cell, Diffuse (drug therapy, metabolism, mortality)
• Male
• Middle Aged
• Prednisone (therapeutic use)
• Prognosis
• Proportional Hazards Models
• Protein Kinase C (metabolism)
• Protein Kinase C beta
• Retrospective Studies
• Tissue Array Analysis
• Vincristine (therapeutic use)