Journal
HUMAN IMMUNOLOGY
Volume 66, Issue 11, Pages 1167-1173Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2005.10.011
Keywords
cervical cancer; adjacent CIN lesion; LOH; HLA class I; loss of expression
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Loss at chromosome 6p2l.3, the human leukocyte antigen (HLA) region, is the main cause of HLA downregulation, occurring in the majority of invasive cervical carcinomas. To identify the stage of rumor development at which HLA class I aberrations occur, we selected 12 patients with cervical carcinoma and adjacent cervical intraepithelial neoplasia (CIN). We investigated HLA class I and beta(2)-Microglobulin expression by immunohiscochemistry in tumor and adjacent CIN. Loss of heterozygosity (LOH) was studied using microsatellite markers covering the HLA region. Fluorescent in Situ hybridization with HLA class I probes was performed to investigate the mechanism of HLA loss. Immunohistochemistry showed absent or weak HLA class I expression in 11/12 cases. In 10 of these 11 cases, downregulation occurred in both tumor and CIN. Only in one case did the concomitant CIN lesion show normal expression. In 9/12 cases, LOH was present for at least one marker in both tumor and CIN, I case showed only LOH in the CIN lesion, and I case showed retention of hererozygosity for all markers in both tumor and CIN. We conclude that HLA class I aberrations Occur early and frequently in cervical carcinogenesis. This might allow premalignant CIN lesions to escape immune surveillance and progress to invasive cancer.
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