Analysis of HLA‐DR expression on keratinocytes in cervical neoplasia

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Abstract
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.