Frequent HLA class I loss is an early event in cervical carcinogenesis.
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 beta2-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.
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands. c.f.w.vermeulen@lumc.nl
Christine F W
CF
Vermeulen
Ekaterina S
ES
Jordanova
Yvon A
YA
Zomerdijk-Nooijen
Natalja T
NT
ter Haar
Alexander A W
AA
Peters
Gert Jan
GJ
Fleuren
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity / Q000276:immunology*; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I