title: FOXP3+ regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence.
abstract: OBJECTIVE
  To characterize clinical features of vulvar Paget's disease, and examine the quantity of immunosuppressive regulatory T-cells in vulvar Paget's tissue.
  
  
  METHODS
  Vulvar Paget's cases from 1992 to 2007 from two institutions were identified by pathology database search. Regulatory T-cells were identified with FOXP3 immunohistochemistry and quantified at the dermal-epidermal junction using image analysis software. Thirteen non-neoplastic inflammatory cases were stained for comparison.
  
  
  RESULTS
  Cases included 33 women treated for primary vulvar Paget's, and 7 referred at recurrence. Of the 24 primary cases with greater than 5 months follow-up, recurrence was documented in 12/24(50%). Eight women (20%) recurred multiple times, but no recurrences were invasive. Significantly more patients with positive margins developed recurrent disease (82% vs 23%, p=0.01). Secondary neoplasms occurred in 10/40(25%). FOXP3+ cells at the dermal-epidermal junction were quantified in 29 primary and 13 recurrent tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin. FOXP3+ cells averaged 66/HPF in primary vulvar Paget's and 66/HPF in recurrent Paget's, compared to 22/HPF in non-neoplastic inflammatory cases (p=0.0003, p=0.001). Primary cases with positive surgical margins had more FOXP3+ cells than those with negative margins (85 vs 49, p=0.01). Recurrent cases with positive margins had more FOXP3+ cells than negative cases (84 vs 33, p=0.06). FOXP3 levels in primary specimens were higher in cases which recurred (78 vs 35, p=0.02).
  
  
  CONCLUSIONS
  Increased regulatory T-cells may be associated with more extensive cases of vulvar Paget's disease that result in positive surgical margins and are associated with recurrence of disease, suggesting immunosuppression as a key factor.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195, USA. jzp@u.washington.edu
authors.forename: Joshua Z
authors.initials: JZ
authors.lastname: Press
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: Allison
authors.forename: Rochelle
authors.initials: R
authors.lastname: Garcia
authors.forename: Elise N
authors.initials: EN
authors.lastname: Everett
authors.forename: Ellen
authors.initials: E
authors.lastname: Pizer
authors.forename: Ron E
authors.initials: RE
authors.lastname: Swensen
authors.forename: Hisham K
authors.initials: HK
authors.lastname: Tamimi
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Gray
authors.forename: William A
authors.initials: WA
authors.lastname: Peters
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Goff
mesh_terms: D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D009364:Neoplasm Recurrence, Local / Q000276:immunology* / Q000473:pathology; D010145:Paget Disease, Extramammary / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014846:Vulvar Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors