The Expression of Protein Kinase C Beta II (PKCβ) by Immunocytochemistry Is Predictive of the Disease Free Survival (DFS) in Diffuse Large B-Cell Lymphoma (DLBCL).

Abstract

PKCβ is a regulatory factor involved in the nuclear factor kappa B pathway. PKCβ gene expression was pinpointed through microarray studies by Shipp et al as one of thirteen, among over six thousand studied genes, to be associated with the probability of cure in DLBCL. The authors also reported a good correlation between PKCβ gene expression and protein expression, and added that in their hands PKCβ protein expression was closely associated with the clinical outcome. Therefore, we analyzed the PKCβ protein expression in 71 samples of DLBCL (44 nodal) by immunocytochemistry. A case was considered positive only if the antigen was unequivocally expressed in the large cells. PKCβ expression was found in 10/71 (14%) of the cases. Some cases had PKCβ expression only in the small lymphocytes, and were considered negative, since this antibody intensely stained mantle zone cells. Most samples had positive internal controls, as both plasma cells and residual mantle zone cells were strongly stained by the antibody. The patients' clinical and biological features were similar in PKCβ positive and negative cases (median age 51 vs. 58 years; male gender 50% vs. 67%; extranodal disease 30% vs. 39%; high IPI 10% vs. 27%; Bcl-2 expression 50% vs. 41%, and CD10 expression 20% vs. 23%). None of these differences were statistically significant. The presence of PKCβ expression was not related to 7-year overall survival (56% vs. 48%, p=0.8). The 5-year event free survival was 54% and 33% in PKCβ negative and positive cases, respectively (p=0,7). A complete remission after an anthracycline based first line chemotherapy was obtained in 75% and 90% of PKCβ negative and positive cases, respectively (p=0,4). However, the 5-year DFS was 80% and 37%, for PKCβ negative and positive cases, respectively (p<0,03). In conclusion, in our cohort of patients the prognostic impact of PKCβ expression was restricted to the DFS.