Membrane PKC-beta 2 protein expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma

The protein kinase C (PKC) plays an important role in the activation and survival of B cells. The purpose of this study was to analyze the clinical significance of PKC-beta 2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL). Tumors from 76 patients with DLBCL who received anthracycline-containing chemotherapy were examined for PKC-beta 2 protein expression by immunohistochemistry. Twenty-six cases (34%) were positive for PKC-beta 2 protein, and 50 (66%) were negative. Patients with PKC-beta-2-positive tumors showed a lower complete remission rate (31 vs 62%; P=0.015) and a lower 5-year disease-free survival (DFS) (30 vs 60%; P=0.03) than the PKC-beta-2-negative group. Overall survival (OS) was significantly lower in patients with the membranous staining pattern of PKC-beta 2 protein when compared to those with PKC-beta-2-negative tumors (14 vs 64%; P=0.005). In patients with low international prognostic index (IPI), those with tumors showing membrane expression of PKC-beta 2 had a significantly inferior DFS and OS (0 vs 79%, P=0.003; 25 vs 80%; P=0.01) compared to PKC-beta-2-negative tumors. In multivariate analysis for OS, the membrane staining of PKC-beta 2 is the strongest independent adverse prognostic factor (OR=3.4, P=0.011). Our results suggest that membrane expression of PKC-beta 2 protein on DLBCL predicts for poor survival, especially in patients with low IPI.