PMID- 24415578
OWN - NLM
STAT- MEDLINE
DCOM- 20140808
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 135
IP  - 4
DP  - 2014 Aug 15
TI  - Alterations in classical and nonclassical HLA expression in recurrent and 
      progressive HPV-induced usual vulvar intraepithelial neoplasia and implications 
      for immunotherapy.
PG  - 830-42
LID - 10.1002/ijc.28713 [doi]
AB  - Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; 
      however, many patients still fail to show clinical responses, which could be 
      explained by an immune escape through alterations in human leukocyte antigen 
      (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n = 
      43) and subsequent recurrent uVIN lesion (n = 20), vaccine-treated uVIN patients 
      (n = 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n = 
      21) and healthy controls (n = 26) for the expression of classical HLA-class I/II 
      and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA). 
      HLA-class I was downregulated in 70% of uVIN patients, including patients with a 
      clinical response to immunotherapy. Downregulation of HLA-class I is probably 
      reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) 
      and HLA-class I could be upregulated in uVIN keratinocyte cultures by interferon 
      gamma. HLA-class I downregulation is more frequently associated with LOH in vulvar 
      carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of 
      uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of 
      uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression 
      was more prominent in vulvar carcinoma. No differences were found between the 
      alterations observed in paired primary and recurrent uVIN. Importantly, 
      downregulation of HLA-B/C in primary uVIN lesions was associated with the 
      development of recurrences and progression to cancer. We conclude that 
      downregulation of HLA is frequently observed in premalignant HPV-induced lesions, 
      including clinical responders to immunotherapy, and is associated with worse 
      clinical outcome. However, in the majority of cases downregulation may still be 
      reversible.
CI  - Copyright (c) 2014 UICC.
FAU - van Esch, E M G
AU  - van Esch EM
AD  - Department of Gynaecology, Leiden University Medical Center, Leiden, The 
      Netherlands; Department of Clinical Oncology, Leiden University Medical Center, 
      Leiden, The Netherlands.
FAU - Tummers, B
AU  - Tummers B
FAU - Baartmans, V
AU  - Baartmans V
FAU - Osse, E M
AU  - Osse EM
FAU - Ter Haar, N
AU  - Ter Haar N
FAU - Trietsch, M D
AU  - Trietsch MD
FAU - Hellebrekers, B W J
AU  - Hellebrekers BW
FAU - Holleboom, C A G
AU  - Holleboom CA
FAU - Nagel, H T C
AU  - Nagel HT
FAU - Tan, L T
AU  - Tan LT
FAU - Fleuren, G J
AU  - Fleuren GJ
FAU - van Poelgeest, M I E
AU  - van Poelgeest MI
FAU - van der Burg, S H
AU  - van der Burg SH
FAU - Jordanova, E S
AU  - Jordanova ES
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140128
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (HLA Antigens)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma/*immunology/therapy/virology
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Regulation
MH  - Gene Expression Regulation, Neoplastic
MH  - Genotype
MH  - HLA Antigens/*metabolism
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Interferon-gamma/metabolism
MH  - Keratinocytes/cytology/drug effects/virology
MH  - Loss of Heterozygosity
MH  - Middle Aged
MH  - Papillomavirus Infections/*immunology/therapy
MH  - Recurrence
MH  - Vulvar Neoplasms/*immunology/therapy/virology
OTO - NOTNLM
OT  - HLA expression
OT  - immunotherapy
OT  - microenvironment
OT  - uVIN
OT  - vulvar carcinoma
EDAT- 2014/01/15 06:00
MHDA- 2014/08/13 06:00
CRDT- 2014/01/14 06:00
PHST- 2013/09/18 00:00 [received]
PHST- 2013/12/17 00:00 [accepted]
PHST- 2014/01/14 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/08/13 06:00 [medline]
AID - 10.1002/ijc.28713 [doi]
PST - ppublish
SO  - Int J Cancer. 2014 Aug 15;135(4):830-42. doi: 10.1002/ijc.28713. Epub 2014 Jan 
      28.