PMID- 15603873
OWN - NLM
STAT- MEDLINE
DCOM- 20050331
LR  - 20071114
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 65
IP  - 12
DP  - 2004 Dec
TI  - High level of aneuploidy of chromosome 6 by FISH analysis of head and neck 
      squamous cell carcinoma: limited applicability of LOH analysis to define HLA 
      loss.
PG  - 1455-62
AB  - Human Leukocyte Antigen (HLA) class I molecules are essential for tumor cell 
      recognition by cytotoxic T cells of the adaptive immune system. Loss of HLA 
      expression provides tumor cells with an escape mechanism to evade the immune 
      system and thus immune therapy. Therefore, HLA loss, and in particular loss of 
      heterozygosity (LOH), is frequently studied in tumors using microsatellite marker 
      LOH analysis. Because LOH analysis detects any allelic imbalance and not just 
      allelic loss, we evaluated the LOH analysis in nine head and neck squamous cell 
      carcinomas (HNSCCs) using fluorescence in situ hybridization (FISH). These tumors 
      were selected from 53 HNSCCs based upon the HLA class I immunohistochemical 
      staining and LOH data. FISH analysis showed that only two tumors with LOH and one 
      without LOH indeed had loss and a normal chromosome 6 copy number, respectively. 
      Strikingly, for the remaining six tumors, LOH analysis did not reflect the genome 
      HLA copy number. We demonstrated that LOH analysis cannot distinguish loss from 
      gain and that the HLA region is not homogeneously affected within a tumor. Tumor 
      heterogeneity and complex aneuploidy in tumors hinder a straightforward 
      interpretation of microsatellite marker analysis. For immune therapy strategies 
      in cancer patients, knowledge of the HLA expression on tumor cells is essential, 
      to which LOH analysis has a limited contribution.
FAU - Koene, Geert J P A
AU  - Koene GJ
AD  - Department of Pathology, University Medical Centre Utrecht, Utrecht, The 
      Netherlands. G.Koene@azu.nl
FAU - Arts-Hilkes, Yvonne H A
AU  - Arts-Hilkes YH
FAU - van Dijk, Anette J G
AU  - van Dijk AJ
FAU - van der Ven, Kevin J W
AU  - van der Ven KJ
FAU - Slootweg, Piet J
AU  - Slootweg PJ
FAU - de Weger, Roel A
AU  - de Weger RA
FAU - Tilanus, Marcel G J
AU  - Tilanus MG
LA  - eng
GR  - 5U24AI49213/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Aneuploidy
MH  - Carcinoma, Squamous Cell/*genetics/*immunology
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Gene Dosage
MH  - HLA Antigens/*genetics/metabolism
MH  - Head and Neck Neoplasms/*genetics/*immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Loss of Heterozygosity
MH  - Microsatellite Repeats
EDAT- 2004/12/18 09:00
MHDA- 2005/04/01 09:00
CRDT- 2004/12/18 09:00
PHST- 2004/04/20 00:00 [received]
PHST- 2004/06/28 00:00 [revised]
PHST- 2004/06/30 00:00 [accepted]
PHST- 2004/12/18 09:00 [pubmed]
PHST- 2005/04/01 09:00 [medline]
PHST- 2004/12/18 09:00 [entrez]
AID - S0198-8859(04)00159-4 [pii]
AID - 10.1016/j.humimm.2004.06.012 [doi]
PST - ppublish
SO  - Hum Immunol. 2004 Dec;65(12):1455-62. doi: 10.1016/j.humimm.2004.06.012.