Variability of Foxp3 Expression in Adult T-Cell Leukemia/Lymphoma (ATLL) in US/Caribbean Cases.
Jinjuan Yao, Susan RS Gottesman, Getinet Ayalew, Albert S Braverman, Constantine A Axiotis. SUNY Downstate Medical Center, Brooklyn, NY; Kings County Hospital Center, Brooklyn, NY
Background: ATLL may be considered a proliferation of neoplastic regulatory T cells (Treg) although how closely they correlate to this normal CD4 T subset which consistently expresses CD25 and Foxp3, is unclear. Some studies show that CD25 and Foxp3 may be inversely related; others have demonstrated heterogeneous Foxp3 expression in ATLL cells suggesting possible loss and independence from Foxp3 expression. Recent studies have suggested that normal Treg cells may, in the approporiate cytokine environment, differentiate to inflammatory effector T cells (ie Th17 cells). The purpose of this study is to characterize the relationship of CD25 and Foxp3 expression in ATLL and to examine whether differentiation into cells with Th17 effector phenotype occurs.
Design: We identified 40 US/Caribbean ATLL patients from 1996 to 2010 who had lymph node, bone marrow and/or skin biopsies available for pathologic review. Eleven patients had biopsies taken at different times during their clinical course. All cases were classified morphologically, and diagnosed as ATLL on the basis of the Shimoyama criteria for clinical and laboratory findings. Immunohistochemistry and/or flow cytometry was performed on all cases for CD25 and Foxp3 utilizing the Foxp3 antibody (clone 221D/D3) which recognizes Foxp3 in the nucleus and does not cross react with other Foxp proteins. Staining for RORγ (transcription factor characteristic of Th17 cells) was performed on Foxp3 negative cases.
Results: Foxp3 was expressed in the majority of tumor cell nuclei in 27/40 cases of ATLL (67.5%). There was no inverse correlation between CD25 and Foxp3 expression. Among 13 Foxp3- cases, 9 showed strong and 4 showed weak (dim) CD25 expression. There was no RORγ expression detected in Foxp3 negative cases. 8/11(72.7%) patients with multiple biopsies showed no change in Foxp3 expression while 3/11(27.2%) patients lost Foxp3 expression.
Conclusions: Foxp3 correlates well with CD25 expression. Foxp3 may be lost in certain cases, either due to the treatment or disease evoloution to a Foxp3 independent differentiation state. There is no preliminary evidence indicating that Foxp3 negative ATLL cells differentiate into Th17 cells.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 228, Tuesday Morning