Expression and genetic analysis of transporter associated with antigen processing in cervical carcinoma

Abstract

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-, β 2-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.