LYMPHOID NEOPLASIA The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation

Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advancedstage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy and radiation. Tissue microarrays were constructed using diagnostic biopsies available in 105 patients and stained with CD4, CD8, CD25, and forkhead/winged helix transcription factor 3 (FOXP3) antibodies. Both cell content and cell distribution were evaluated. For all antibodies, there were cases with a predominant intrafollicular or perifollicular localization of cells (follicular pattern) while others displayed a diffuse pattern. The median follow-up of living patients was 17.1 years. The International Prognostic Index score predicted overall survival (OS; P .004) but not risk of transformation (RT). Cell content did not impact survival, while immunoarchitectural patterns of CD4/ CD8 were significant for progression-free survival (PFS; P .056), CD25 for both PFS and OS (P .002 and P .024, respectively), and FOXP3 predicted PFS, OS, and RT (P .001, P < .001 and p .002, respectively). A Cox multivariate model showed both International Prognostic Index score and FOXP3 pattern were independent predictors of OS (P .008 and P < .001, respectively), while only FOXP3 pattern predicted RT (P .004). We conclude that FOXP3 cell distribution significantly predicts survival and RT in FL. (Blood. 2010;115: 289-295)