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

Abstract

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-b), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P ¼ 0.025) or PKC-b (P ¼ 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-b had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P ¼ 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-b was an independent predictor of poor overall survival (P ¼ 0.035). Cyclin D2 and PKC-b expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.

PKC-beta II expression has prognostic impact in nodal diffuse large B-cell lymphoma

“…Patients in the high-risk group presented a similar trend, but the difference in survival did not reach statistical significance. 8 Although extranodal lymphomas were included, these findings are very similar to the results of the present study. In both cases, however, the lack of statistical significance might have been due to the smaller number of patients available for analysis in the high-risk IPI group.…”

“…The different cutoff points used in these two studies appear to be overly dependent on each data set. When our cases were reassessed using the 50% cutoff, 8 PKC-beta II lost its prognostic meaning for the 5-year overall survival (55 vs 50% for negative and positive cases, P ¼ 0.53) and the 5-year EFS (45 vs 43% for negative and positive cases, P ¼ 0.82). As in all studies involving immnophenotyping of lymphomas, a better standardization of the methodology is clearly needed if these methods are ever to influence clinical decisions.…”

“…3,4 Two studies have recently analyzed the prognostic impact of PKC-beta II expression by immunohistochemistry in patients with DLBCL, with conflicting results. 8,9 While Hans et al 8 verified that the expression of PKC-beta II imparted a bad prognosis to the patients, the study by Sáez et al 9 found no association between PKC-beta II expression and clinical outcome in these patients.…”

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

“…[54][55][56][57] The expression of cyclin D2 or CD44 is also correlated with a poor prognosis in patients with diffuse large B-cell lymphoma. 19,58 Therefore, although there is discrepancy in TIMP-1 signaling pathways depending on cell type,TIMP-1 appears to inhibit apoptosis by activating the PI-3 kinase/Akt and/or STAT3 signaling cascades. The activation of these signaling pathways regulates BCL-2 family members, especially involving BCL-X L resulting in inhibition of caspase activation and thereby inhibition of apoptosis.…”

“…Cases were considered positive if 30% or more of the tumor cells were stained with an antibody other than anti-TIMP-1 antibody. Based on previous immunohisto- TIMP-1 expression in diffuse large B-cell lymphoma J-W Choi et al chemical studies, [19][20][21][22] we chose a uniform cutoff of 30%. However, for TIMP-1, a cutoff of greater than 20% was used because its secretory properties and low level of expression within cells.…”