Analysis of HLA-DR expression on keratinocytes in cervical neoplasia.
We have investigated the expression in vivo and in vitro of HLA-DR in pre-invasive squamous-cell neoplasia of the uterine cervix. Immunohistochemistry of cervical biopsies demonstrated HLA-DR expression by cervical keratinocytes in 50% of cases of high-grade squamous intra-epithelial neoplasia, although the molecule was rarely expressed in low-grade squamous intra-epithelial neoplasia and was absent from normal ectocervical cells. HLA-DR-positive high-grade lesions were associated with significantly greater numbers of T lymphocytes in the immediately sub-epithelial stroma than were the HLA-DR-negative high-grade lesions. In vitro HLA-DR expression was absent from normal ectocervical epithelium, and from the HPV type 16 containing cell lines W12 (representing low-grade squamous intra-epithelial neoplasia) and CaSki and SiHa (each representing high-grade squamous intra-epithelial neoplasia), both in monolayer and in organotypic raft culture. HLA-DR expression was induced in all cell types following recombinant interferon gamma treatment. Our data suggest that the expression of HLA-DR by keratinocytes in some high-grade cervical lesions in vivo may be due to local induction of the molecule by pro-inflammatory cytokines released by immunocompetent cells. The functional significance of HLA-DR positivity in enabling an effective host immune response to neoplastic cervical keratinocytes remains unclear.
Coleman
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Department of Pathology, University of Cambridge, UK.
Stanley
M A
MA
D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology*; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology
D006684:HLA-DR Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma