title: Expression of intratumoral forkhead box protein 3 in posttransplant lymphoproliferative disorders: clinical features and survival outcomes.
abstract: BACKGROUND
  The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.
  
  
  METHODS
  Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.
  
  
  RESULTS
  Based on a cutoff level of 29 FoxP3 cells per mm, most (80%) of the PTLDs were FoxP3. Forty-seven of 74 PTLDs displayed no FoxP3 cells at all. The frequency of FoxP3 cells did not influence median overall survival. The FoxP3 PTLDs were more frequently of T-cell phenotype (P = 0.04), located at the graft (P = 0.03), occurred earlier after transplantation (P = 0.04), were more likely to develop in lung recipients (P = 0.04), and in patients that had received anti-T-cell globulin as induction therapy (P = 0.02). The FoxP3 PTLDs were associated with hepatitis C seropositivity (P = 0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.
  
  
  CONCLUSIONS
  Our findings suggest that intratumoral FoxP3 Tregs do not influence survival in patients with PTLD. FoxP3 Tregs are rare in PTLD, possibly because of heavy immunosuppression.
authors.affiliation: 1 Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Uppsala, Sweden. 2 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 3 Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 4 Halmstad Hospital, Halmstad, Sweden. 5 Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 6 Section of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Berglund
authors.forename: Amelie
authors.initials: A
authors.lastname: Kinch
authors.forename: Elin
authors.initials: E
authors.lastname: Edman
authors.forename: Carin
authors.initials: C
authors.lastname: Backlin
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.forename: Daniel
authors.initials: D
authors.lastname: Molin
authors.forename: Karlis
authors.initials: K
authors.lastname: Pauksens
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications / Q000276:immunology* / Q000401:mortality; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents