Expression of AIF and HtrA2/Omi in small lymphocytic lymphoma and diffuse large B-cell lymphoma

Context.-The pathogenesis of non-Hodgkin lymphoma may involve deregulation of apoptosis. In response to apoptotic stimuli, several proapoptotic proteins are released into the cytoplasm from the mitochondria, including second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein binding protein with low p/ (Smac/ DIABLO), apoptosis-inducing factor (AIF), and high temperature requirement protein A2 (HtrA2/Omi). Apoptosisinducing factor promotes apoptosis through a caspaseindependent pathway, while Smac/DIABLO and HtrA2/ Omi do so through both caspase-dependent and caspaseindependent pathways. Smac/DIABLO was reported to be strongly positive in diffuse large B-cell lymphoma (DLBCL) and virtually absent in small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL). Little is known about the expression of AIF and HtrA2/Omi in lymphomas. Objective.-To evaluate the expression of AIF and HtrA2/Omi in SLL and DLBCL. Design.-Twenty-three DLBCLs, 20 SLLs/CLLs, and 10 benign lymph nodes were evaluated for AIF and HtrA2/ Omi expression by immunohistochemical staining. Results.-Apoptosis-inducing factor was strongly and diffusely expressed in 19 of 23 (83%) cases of DLBCL with comparable expression pattern between germinal centerlike and non-germinal center-like subgroups. Apoptosisinducing factor was weakly positive in 15 of 20 (75%) cases of SLL/CLL with increased intensity in pseudofollicles. In contrast, HtrA2/Omi was weakly expressed in SLL/ CLL (17 of 20; 85%) and DLBCL (18 of 23; 78%). Conclusions.-The different expression level and pattern of AIF and HtrA2/Omi in SLL/CLL and DLBCL may suggest different apoptotic mechanisms involved in the pathogenesis and prognosis of these diseases. HtrA2/Omi does not appear to be a major player in the regulation of apoptosis of DLBCL and SLL/CLL.