PMID- 30274932
OWN - NLM
STAT- MEDLINE
DCOM- 20190123
LR  - 20190123
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Linking)
VI  - 151
IP  - 3
DP  - 2018 Dec
TI  - The immune cell infiltrate in the microenvironment of vulvar Paget disease.
PG  - 453-459
LID - S0090-8258(18)31245-9 [pii]
LID - 10.1016/j.ygyno.2018.09.026 [doi]
AB  - BACKGROUND: Non-invasive vulvar Paget disease (VPD) is a rare skin disorder
      mainly affecting elderly women. Recently, the immune modulator imiquimod was
      reported as an effective treatment option. Knowledge about the immune
      microenvironment of VPD is lacking. METHODS: This study investigates the basic
      characteristics of the immune infiltrate in VPD (n=10); moreover the influence of
      imiquimod was studied (n=6). Immunohistochemistry for CD4, CD8, CD14, CD20, CD56 
      and FoxP3 was performed. The infiltrates of VPD were compared to vulvar
      high-grade squamous cell intraepithelial lesions (HSIL) (n=43), a HPV induced
      vulvar premalignancy with known response to imiquimod cream, and healthy controls
      (n=30). Immune cell counts in samples taken before and after treatment were
      compared. RESULTS: The microenvironment in VPD differs from the healthy vulvar
      skin and vulvar HSIL. VPD is characterized by a decrease in immune cells in the
      epithelium and an abundant number of immune cells in the stroma, consisting
      predominantly of T cells. The intraepithelial CD8+/Foxp3+ ratio and number of
      CD56+ increased after imiquimod therapy, whereas the numbers of CD14+ cells
      decreased which may point to a treatment-induced type 1 immune response.
      CONCLUSIONS: The epithelium in VPD contains less immune cells, but a dense
      stromal immune infiltrate. Changes in immune cell counts after immune modulation 
      in relation to clinical responses should be further investigated.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - van der Linden, Michelle
AU  - van der Linden M
AD  - Department of Obstetrics & Gynaecology, Radboud university Medical Centre,
      Nijmegen, the Netherlands. Electronic address:
      Michelle.vanderLinden@radboudumc.nl.
FAU - van Esch, Edith
AU  - van Esch E
AD  - Department of Obstetrics & Gynaecology, Radboud university Medical Centre,
      Nijmegen, the Netherlands. Electronic address: Edith.vanEsch@radboudumc.nl.
FAU - Bulten, Johan
AU  - Bulten J
AD  - Department of Pathology, Radboud University Medical Centre, Nijmegen, the
      Netherlands. Electronic address: Hans.Bulten@radboudumc.nl.
FAU - Dreef, Enno
AU  - Dreef E
AD  - Department of Pathology, Leiden University Medical Centre, the Netherlands.
      Electronic address: E.J.Dreef@lumc.nl.
FAU - Massuger, Leon
AU  - Massuger L
AD  - Department of Obstetrics & Gynaecology, Radboud university Medical Centre,
      Nijmegen, the Netherlands. Electronic address: Leon.Massuger@radboudumc.nl.
FAU - van der Steen, Sophieke
AU  - van der Steen S
AD  - Department of Obstetrics & Gynaecology, Radboud university Medical Centre,
      Nijmegen, the Netherlands. Electronic address:
      Sophieke.vanderSteen@radboudumc.nl.
FAU - Bosse, Tjalling
AU  - Bosse T
AD  - Department of Pathology, Leiden University Medical Centre, the Netherlands.
      Electronic address: T.Bosse@lumc.nl.
FAU - de Hullu, Joanne
AU  - de Hullu J
AD  - Department of Obstetrics & Gynaecology, Radboud university Medical Centre,
      Nijmegen, the Netherlands. Electronic address: Joanne.deHullu@radboudumc.nl.
FAU - van Poelgeest, Mariette
AU  - van Poelgeest M
AD  - Department of Gynaecology, Leiden University Medical Centre, the Netherlands.
      Electronic address: M.I.E.van_Poelgeest@lumc.nl.
LA  - eng
PT  - Journal Article
DEP - 20180928
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Middle Aged
MH  - Paget Disease, Extramammary/drug therapy/*immunology
MH  - Treatment Outcome
MH  - Tumor Microenvironment
MH  - Vulvar Neoplasms/drug therapy/*immunology
OTO - NOTNLM
OT  - *Imiquimod
OT  - *Immune infiltrate
OT  - *Vulvar Paget disease
EDAT- 2018/10/03 06:00
MHDA- 2019/01/24 06:00
CRDT- 2018/10/03 06:00
PHST- 2018/07/08 00:00 [received]
PHST- 2018/09/01 00:00 [revised]
PHST- 2018/09/23 00:00 [accepted]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2019/01/24 06:00 [medline]
PHST- 2018/10/03 06:00 [entrez]
AID - S0090-8258(18)31245-9 [pii]
AID - 10.1016/j.ygyno.2018.09.026 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2018 Dec;151(3):453-459. doi: 10.1016/j.ygyno.2018.09.026. Epub
      2018 Sep 28.