Prevalent Expression of IL-21 Receptor in Follicular Lyphoma and Potential Association with Poor-Outcome Disease.
Soma Sikdar, Brianne Wood, Abdulmohsen Alhejaily, Tara Baetz, David LeBrun. Queen's University, Kingston, ON, Canada; Kingston General Hospital, ON, Canada
Background: Interleukin-21 (IL-21), a recently discovered member of the common γ-chain family of cytokines, can enhance anti-tumor immunity and induce apoptosis in B lymphocytes. Exogenous, recombinant IL-21 shows promise in cancer therapy. Since IL-21 can induce apoptosis in follicular lymphoma (FL) cells mediated by the IL-21 receptor (IL21R), differential expression of IL21R in FL biopsy samples may predict responses to IL-21 therapy or define biologically- or clinically-important subsets of FL cases. Therefore, we used immunohistochemistry to evaluate the expression of IL21R in 118 FL biopsy samples and correlated these results with pathological and clinical features, including overall survival.
Design: Formalin-fixed, paraffin-embedded biopsy samples from subjects from whom clinical data were retrievable were represented in tissue microarrays. Histological sections were immunostained for IL21R using a monoclonal antibody the specificity of which was confirmed using a blocking peptide. Staining in follicle centers was scored visually as low, intermediate or high by two pathologists; consensus results were determined without knowledge of the other data. Associations were investigated using Fisher's exact test or the Kaplan-Meier method with SPSS software.
Results: IL21R expression was scored as low in 23 cases, intermediate in 47 and high in 48. Relative to IL21R-intermediate or -high cases, IL21R-low cases were less likely to have elevated serum LDH (p=0.11), B-symptoms (p=0.15) or an associated component of diffuse large B-cell lymphoma (p=0.099), and enjoyed a trend towards longer overall survival (p=0.24). No clear associations were observed with histological grade, proliferation index, age, sex, ECOG stage, hemoglobin, performance status or number of involved nodal sites.
Conclusions: Our results based on the largest survey to date indicate prevalent expression of IL21R in FL and suggest that abundant expression is more prevalent among cases with relatively unfavorable clinical and pathological features. Therefore, therapy with exogenous IL21 may have a particular role in those FL cases that do relatively poorly on current therapeutic regimens.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 204, Wednesday Afternoon