PMID- 17316446
OWN - NLM
STAT- MEDLINE
DCOM- 20070319
LR  - 20210103
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 7
DP  - 2007 Feb 22
TI  - HNPCC versus sporadic microsatellite-unstable colon cancers follow different 
      routes toward loss of HLA class I expression.
PG  - 33
AB  - BACKGROUND: Abnormalities in Human Leukocyte Antigen (HLA) class I expression are 
      common in colorectal cancer. Since HLA expression is required to activate tumor 
      antigen-specific cytotoxic T-lymphocytes (CTL), HLA class I abnormalities 
      represent a mechanism by which tumors circumvent immune surveillance. Tumors with 
      high microsatellite instability (MSI-H) are believed to face strong selective 
      pressure to evade CTL activity since they produce large amounts of immunogenic 
      peptides. Previous studies identified the prevalence of HLA class I alterations 
      in MSI-H tumors. However, those reports did not compare the frequency of 
      alterations between hereditary and sporadic MSI-H tumors neither the mechanisms 
      that led to HLA class I alterations in each subgroup. METHODS: To characterize 
      the HLA class I expression among sporadic MSI-H and microsatellite-stable (MSS) 
      tumors, and HNPCC tumors we compared immunohistochemically the expression of HLA 
      class I, beta2-microglobulin (beta2m), and Antigen Processing Machinery (APM) 
      components in 81 right-sided sporadic and 75 HNPCC tumors. Moreover, we 
      investigated the genetic basis for these changes. RESULTS: HLA class I loss was 
      seen more frequently in MSI-H tumors than in MSS tumors (p < 0.0001). Distinct 
      mechanisms were responsible for HLA class I loss in HNPCC and sporadic MSI-H 
      tumors. Loss of HLA class I expression was associated with beta2m loss in HNPCC 
      tumors, but was correlated with APM component defects in sporadic MSI-H tumors (p 
      < 0.0001). In about half of the cases, loss of expression of HLA class I was 
      concordant with the detection of one or more mutations in the beta2m and APM 
      components genes. CONCLUSION: HLA class I aberrations are found at varying 
      frequencies in different colorectal tumor types and are caused by distinct 
      genetic mechanisms. Chiefly, sporadic and hereditary MSI-H tumors follow 
      different routes toward HLA class I loss of expression supporting the idea that 
      these tumors follow different evolutionary pathways in tumorigenesis. The 
      resulting variation in immune escape mechanisms may have repercussions in tumor 
      progression and behavior.
FAU - Dierssen, Jan Willem F
AU  - Dierssen JW
AD  - Department of Pathology, Leiden University Medical Center, Leiden, The 
      Netherlands. JWFDierssen@gmail.com <JWFDierssen@gmail.com>
FAU - de Miranda, Noel F C C
AU  - de Miranda NF
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - van Puijenbroek, Marjo
AU  - van Puijenbroek M
FAU - Cornelisse, Cees J
AU  - Cornelisse CJ
FAU - Fleuren, Gert Jan
AU  - Fleuren GJ
FAU - van Wezel, Tom
AU  - van Wezel T
FAU - Morreau, Hans
AU  - Morreau H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070222
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
SB  - IM
MH  - Aged
MH  - Colonic Neoplasms/*genetics/*immunology
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics/*immunology
MH  - Female
MH  - Genes, MHC Class I/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - *Microsatellite Instability
MH  - Middle Aged
MH  - Tumor Escape
PMC - PMC1808468
EDAT- 2007/02/24 09:00
MHDA- 2007/03/21 09:00
PMCR- 2007/02/22
CRDT- 2007/02/24 09:00
PHST- 2006/10/20 00:00 [received]
PHST- 2007/02/22 00:00 [accepted]
PHST- 2007/02/24 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2007/02/24 09:00 [entrez]
PHST- 2007/02/22 00:00 [pmc-release]
AID - 1471-2407-7-33 [pii]
AID - 10.1186/1471-2407-7-33 [doi]
PST - epublish
SO  - BMC Cancer. 2007 Feb 22;7:33. doi: 10.1186/1471-2407-7-33.