PMID- 17382375
OWN - NLM
STAT- MEDLINE
DCOM- 20070619
LR  - 20221207
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 105
IP  - 3
DP  - 2007 Jun
TI  - Expression and genetic analysis of transporter associated with antigen processing 
      in cervical carcinoma.
PG  - 593-9
AB  - OBJECTIVE: Transporter associated with antigen processing (TAP) loss causes human 
      leukocyte antigen (HLA) class I downregulation which is frequently found in 
      cervical carcinomas and their precursors. HLA class I molecules activate T-cells 
      by antigen presentation and are therefore essential for immunological 
      surveillance. To add to the hitherto limited knowledge of molecular mechanisms 
      underlying TAP loss, we investigated TAP expression, loss of heterozygosity (LOH) 
      and possible TAP mutations. METHODS: Twenty-three cervical carcinomas and 
      adjacent precursor lesions were stained with HLA-A-, HLA-B/C-, beta2 
      -microglobulin-, TAP1- and TAP2- antibodies. In order to separate tumour and 
      non-tumour cells, cervical carcinoma samples were sorted by flow-cytometry and 
      were subsequently analysed for LOH with 3 markers in the TAP region on chromosome 
      6p21.3. Mutation analysis of the complete TAP1 gene was performed. RESULTS: 
      Aberrant TAP1 expression was detected in 10/23 cervical carcinoma lesions and in 
      5/10 adjacent cervical intraepithelial neoplasia (CIN) lesions. All the lesions 
      with low TAP expression also had reduced HLA class I expression. LOH was found in 
      7 out of 10 lesions with TAP loss. Mutation analysis detected no aberrations, but 
      identified a polymorphism in the 5'-untranslated region (UTR) of the TAP1 gene in 
      two lesions. CONCLUSIONS: This study shows that defective TAP expression in 
      cervical carcinoma is often associated with LOH in the TAP region but not with 
      mutations in the TAP1 gene.
FAU - Vermeulen, Christine F W
AU  - Vermeulen CF
AD  - Department of Pathology, Leiden University Medical Centre, L1-Q, 2300 RC Leiden, 
      The Netherlands.
FAU - Jordanova, Ekaterina S
AU  - Jordanova ES
FAU - ter Haar, Natalja T
AU  - ter Haar NT
FAU - Kolkman-Uljee, Sandra M
AU  - Kolkman-Uljee SM
FAU - de Miranda, Noel F
AU  - de Miranda NF
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Peters, Alexander A W
AU  - Peters AA
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
LA  - eng
GR  - R01 CA67108/CA/NCI NIH HHS/United States
GR  - R01CA110249/CA/NCI NIH HHS/United States
GR  - R01CA113861/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070326
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (transporter associated with antigen processing (TAP))
SB  - IM
MH  - ATP-Binding Cassette Transporters/biosynthesis/*genetics/immunology
MH  - DNA Mutational Analysis
MH  - Female
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class I/biosynthesis/genetics/immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - Loss of Heterozygosity
MH  - Neoplasm Staging
MH  - Paraffin Embedding
MH  - Uterine Cervical Neoplasms/*genetics/*immunology/pathology
MH  - Uterine Cervical Dysplasia/*genetics/*immunology/pathology
EDAT- 2007/03/27 09:00
MHDA- 2007/06/20 09:00
CRDT- 2007/03/27 09:00
PHST- 2006/12/05 00:00 [received]
PHST- 2007/02/01 00:00 [revised]
PHST- 2007/02/12 00:00 [accepted]
PHST- 2007/03/27 09:00 [pubmed]
PHST- 2007/06/20 09:00 [medline]
PHST- 2007/03/27 09:00 [entrez]
AID - S0090-8258(07)00140-0 [pii]
AID - 10.1016/j.ygyno.2007.02.016 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2007 Jun;105(3):593-9. doi: 10.1016/j.ygyno.2007.02.016. Epub 2007 
      Mar 26.