Assessing DcR3 expression in relation to survivin and other prognostic factors in B cell non-Hodgkin’s lymphoma

Abstract

The soluble decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily whose overexpression has been observed in several human malignancies. Survivin is one of the inhibitors of apoptosis proteins that are thought to play an important role in the pathogenesis of malignancies. We aimed to evaluate the expression of DcR3 in relation to survivin in B cell non-Hodgkin`s lymphoma (NHL) and then we focused on patients with diffuse large B cell non-Hodgkin's lymphoma (DLBCL) (50 cases) and correlated DcR3 expression with survivin expression and other prognostic parameters. Fifteen subjects with reactive lymphoid hyperplasia were included as controls. The expression of DcR3 and survivin were analyzed by immunohistochemistry on formalin-fixed paraffin-embedded lymph node sections from 80 cases of B cell NHL and 15 controls. Bone marrow biopsy sections of patients were also immunostained with the previous markers. DcR3 expression was found in 32.5% of B cell NHL patients versus 6.7% of controls (p <0.001) and was associated with the aggressive/highly aggressive subtypes. DcR3 was strongly expressed in 30% of DLBCL patients, where it was associated with survivin expression, high international prognostic index (IPI), the presence of extra nodal disease, ECOG performance status >1, reduced remission rates and shorter event-free survival. The expression of survivin was 40% in B cell NHL patients versus 13.3% in the control group (p <0.001). The expression of survivin in aggressive/highly aggressive B cell NHL was significantly higher than that in indolent B cell NHL. Survivin expression has been detected in 44% of the DLBCL patients and was associated with their clinical stage and shorter event-free survival (p = 0.026). Bone marrow biopsy sections from DLBCL patients showed significant DcR3 and survivin over expressions in sections with infiltration by lymphoma cells than sections with no infiltration. DcR3 expression was associated with other prognostic factors including survivin, reduced remission rates, and shorter event-free survival. Survivin is closely related to aggressive/highly aggressive subtypes of B cell NHL and is associated with shorter event-free survival. Both DcR3 and survivin expressions on bone marrow sections can be of help in diagnosing bone marrow infiltration.