Frequent HLA class I loss is an early event in cervical carcinogenesis

Christine F.W. Vermeulen*, Ekaterina S. Jordanova, Yvon A. Zomerdijk-Nooijen, Natalja T. Ter Haar, Alexander A.W. Peters, Gert Jan Fleuren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Loss at chromosome 6p21.3, 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 tumor 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 β2-microglobulin expression by immunohistochemistry 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, 1 case showed only LOH in the CIN lesion, and 1 case showed retention of heterozygosity 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.

Original languageEnglish
Pages (from-to)1167-1173
Number of pages7
JournalHuman Immunology
Issue number11
Publication statusPublished - 1 Nov 2005

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