PMID- 16571417
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20221207
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 66
IP  - 11
DP  - 2005 Nov
TI  - Frequent HLA class I loss is an early event in cervical carcinogenesis.
PG  - 1167-73
AB  - 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.
FAU - Vermeulen, Christine F W
AU  - Vermeulen CF
AD  - Department of Pathology, Leiden University Medical Centre, Leiden, The 
      Netherlands. c.f.w.vermeulen@lumc.nl
FAU - Jordanova, Ekaterina S
AU  - Jordanova ES
FAU - Zomerdijk-Nooijen, Yvon A
AU  - Zomerdijk-Nooijen YA
FAU - ter Haar, Natalja T
AU  - ter Haar NT
FAU - Peters, Alexander A W
AU  - Peters AA
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
LA  - eng
PT  - Journal Article
DEP - 20060104
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Carcinoma, Squamous Cell/genetics/*immunology/pathology
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Female
MH  - HLA Antigens/*genetics/*metabolism
MH  - Histocompatibility Antigens Class I/*genetics/*metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Loss of Heterozygosity/*immunology
MH  - Time Factors
MH  - Uterine Cervical Neoplasms/genetics/*immunology/pathology
MH  - Uterine Cervical Dysplasia/genetics/*immunology/pathology
EDAT- 2006/03/31 09:00
MHDA- 2009/06/12 09:00
CRDT- 2006/03/31 09:00
PHST- 2005/07/15 00:00 [received]
PHST- 2005/10/13 00:00 [accepted]
PHST- 2006/03/31 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
PHST- 2006/03/31 09:00 [entrez]
AID - S0198-8859(05)00437-4 [pii]
AID - 10.1016/j.humimm.2005.10.011 [doi]
PST - ppublish
SO  - Hum Immunol. 2005 Nov;66(11):1167-73. doi: 10.1016/j.humimm.2005.10.011. Epub 
      2006 Jan 4.