Expression and genetic analysis of transporter associated with antigen processing in cervical carcinoma.
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.
Vermeulen
Christine F W
CF
Department of Pathology, Leiden University Medical Centre, L1-Q, 2300 RC Leiden, The Netherlands.
Jordanova
Ekaterina S
ES
ter Haar
Natalja T
NT
Kolkman-Uljee
Sandra M
SM
de Miranda
Noel F
NF
Ferrone
Soldano
S
Peters
Alexander A W
AA
Fleuren
Gert Jan
GJ
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D004252:DNA Mutational Analysis; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C477327:transporter associated with antigen processing (TAP)