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 I (Smac/DIABLO), apoptosis-inducing factor (AIF), and high temperature requirement protein A2 (HtrA2/Omi). Apoptosis-inducing factor promotes apoptosis through a caspase-independent pathway, while Smac/DIABLO and HtrA2/Omi do so through both caspase-dependent and caspase-independent 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.
To evaluate the expression of AIF and HtrA2/Omi in SLL and DLBCL.
Twenty-three DLBCLs, 20 SLLs/CLLs, and 10 benign lymph nodes were evaluated for AIF and HtrA2/Omi expression by immunohistochemical staining.
Apoptosis-inducing factor was strongly and diffusely expressed in 19 of 23 (83%) cases of DLBCL with comparable expression pattern between germinal center-like and non-germinal center-like subgroups. Apoptosis-inducing 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%).
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.