FOXP3+ regulatory T-cells are abundant in vulvar Paget's disease and are associated with recurrence

Gynecol Oncol. 2011 Feb;120(2):296-9. doi: 10.1016/j.ygyno.2010.10.019.


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.

MeSH terms

  • Aged
  • Female
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Immunohistochemistry
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / pathology
  • Paget Disease, Extramammary / immunology*
  • Paget Disease, Extramammary / pathology
  • Paget Disease, Extramammary / surgery
  • T-Lymphocytes, Regulatory / immunology*
  • Vulvar Neoplasms / immunology*
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / surgery


  • FOXP3 protein, human
  • Forkhead Transcription Factors