Abstract
Protein Kinase C (PKC) is an important enzyme family. Twelve different isozymes have been described, which are implicated in diverse cell responses. Recently, studies have begun to define isoform-specific functions of PKC, and PKC beta II seems to play an antiapoptotic role. PKC beta II expression was analyzed by immunohistochemistry in 119 tumor samples of patients with lymphoid malignancies. The median age of the group was 55 years (range 14–85 y). Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue, using the labeled avidin-biotin immuno-peroxidase complex method on the Ventana Benchmark automated immunostainer (Ventana Medical Systems, S.A., Illkirch, France). The sections were incubated with primary antibody (polyclonal antibody cPKC ßII (C-1): sc-210, Santa Cruz Biotechnology, Inc.) for 32 min at 1/100 dilution. The intensity of cytoplasmic and membrane immunostaining was assessed semi-quantitatively by two pathologists independently. Cases were considered “negative” when <10% of cells were stained, and “positive” when ≥10% of tumor cells showed cytoplasmic or membrane staining. Diffuse or heterogeneous staining was also specified.
Intense and diffuse staining was observed in all mantle cell lymphomas (13 cases, 100%), and chronic lymphocytic lymphomas (CCL) (6 cases, 100%). PKC beta II was positive too in most follicular lymphomas (10 cases out of 11, 91%), although the pattern and the intensity of the staining were variable in accordance with the degree of lymphomatous infiltration. Indeed, in the same lymph node, the follicular lymphomatous areas were constantly labelled, whereas residual germinal centers remained negative. A majority of angioimmunoblastic T-cell lymphomas, lymphoblastic T-cell lymphomas and Marginal Zone/MALT lymphomas were labelled with anti-PKC beta II antibody, but the pattern of expression was more heterogeneous in these subtypes. A minority of diffuse large B-cell lymphomas expressed PKC beta II (8 out of 22 cases, including 4 with weak staining). Nearly all plasma cell neoplasms were negative. Nevertheless, 2 cases out of 16 (13%) displayed a diffuse moderate staining. In peripheral T-cell lymphomas, staining for PKC beta II was less frequent, as well as in primary cutaneous B and T lymphomas and pseudo-lymphomas. None of the cases of Hodgkin’s disease (13 cases) and anaplastic large cell lymphoma (5 cases) expressed PKC beta II. However, most of the numerous reactive cells were strongly stained.
In conclusion, the intensity and the staining pattern of anti-PKC beta II antibody varied greatly according to the type lymphoid malignancy. These results highlight a significant correlation between PKC beta II expression and some particular type of lymphomas. In our series, the highest level of expression was found in mantle cell lymphomas and CLL.
Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities
