title: The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation.
abstract: Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage 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.
authors.affiliation: Pathology and Laboratory Medicine, BC Cancer Agency Center for Lymphoid Cancers, Vancouver, BC, Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Abdulwahab
authors.initials: A
authors.lastname: Al-Tourah
authors.forename: Karamjit
authors.initials: K
authors.lastname: Gill
authors.forename: Richard
authors.initials: R
authors.lastname: Klasa
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D015703:Antigens, CD; D016516:CD4-CD8 Ratio; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008224:Lymphoma, Follicular / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors