Abundant Expression of IL-21 Receptor in Follicular Lymphoma Is Associated with More Aggressive Disease
Soma Sikdar, Suk Jin Choi, Shakeel Virk, Brianne Wood, Abdulmohsen Alhejaily, Tara Baetz, David LeBrun. Queen's University, Kingston, ON, Canada; Kingston General Hospital, Kingston, ON, Canada
Background: Interleukin IL-21 (IL-21), a recently discovered cytokine, can induce apoptosis in follicular lymphoma (FL). Therefore, differential expression of the IL-21 receptor (IL-21R) in FL biopsy samples may define biologically- or clinically-important subsets of FL cases or eventually be useful in predicting responses to therapy with recombinant IL-21. We have correlated expression of IL-21R in FL biopsy samples with pathological and clinical features so as to define clinically and biologically distinct disease subsets.
Design: Paraffin-embedded samples from 114 cases of FL were represented in tissue microarrays (TMAs) and IL-21R was quantified selectively in neoplastic B lymphocytes using quantitative, multiplex immunofluorescence microscopy and AQUA software. X-tile software was used to divide the cohort into training and validation sets and establish an optimal cutpoint to divide the training set into IL-21R-low and -high subsets.
Results: Of the 57 cases in the validation set, 13 were IL-21R-high. These showed a trend towards reduced survival (P= 0.083) that persisted when the analysis was repeated after excluding the 10 cases in which a component of diffuse large B-cell lymphoma (DLBCL) was present in the biopsy (P=0.04, see figure). High IL-21R expression was associated with an elevated risk of death within 5 years (P=0.015), the presence of a DLBCL component (P=0.028) and rapid cell proliferation indicated by prevalent expression of Ki-67 (P=0.019). Potential associations were observed with high-risk FLIPI score (P=0.077) and low hemoglobin (P=0.054).
Conclusions: Our results based on the largest survey to date suggest that high IL-21R expression by FL cells is associated with aggressive disease and unfavourable clinical outcome. IL-21R on FL cells could respond to IL-21 produced by infiltrating CD4-positive cells and promote survival or proliferation. Conversely, our results also raise the possibility that therapy with exogenous IL-21 may have a particular role in FL cases that do relatively poorly on current therapeutic regimens. AQUA-based quantification of IL-21R is potentially useful in predicting clinical responses to therapy with exogenous IL-21.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 219, Monday Morning