PMID- 19462419
OWN - NLM
STAT- MEDLINE
DCOM- 20091009
LR  - 20201222
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 219
IP  - 1
DP  - 2009 Sep
TI  - MUTYH-associated polyposis carcinomas frequently lose HLA class I expression - a 
      common event amongst DNA-repair-deficient colorectal cancers.
PG  - 69-76
LID - 10.1002/path.2569 [doi]
AB  - Human leukocyte antigen (HLA) class I expression defects frequently occur in 
      colorectal cancers bearing mismatch repair (MMR) deficiencies and are interpreted 
      as immune evasion mechanisms to avoid cancer cell recognition and elimination by 
      the immune system. MMR-deficient tumours are thought to be more prone to lose HLA 
      class I expression, due to their frequent generation of aberrant peptides which 
      can stimulate a cytotoxic T-cell-mediated response. MUTYH-associated polyposis 
      (MAP) is a colorectal cancer syndrome caused by defects in the MUTYH DNA repair 
      enzyme. Impairment of MUTYH activity could lead to a surplus of mutated peptides 
      which would be presented to cytotoxic T-cells through the HLA class I molecules. 
      We have studied the frequency of HLA class I expression defects in MAP carcinomas 
      and have compared it to those observed in MMR-deficient and -proficient 
      colorectal tumours. Immunohistochemical detection of the expression of HLA class 
      I, beta2-microglobulin (beta2m), and antigen-processing machinery molecules was 
      performed in 37 primary MAP carcinomas and nine metastases resected from 29 MAP 
      patients. Furthermore, we sequenced the beta2m, TAP1, and TAP2 genes. Defects in 
      HLA class I expression were detected in 65% of primary MAP carcinomas, affecting 
      72% of patients. HLA class I expression abnormalities were often concomitant with 
      beta2m expression loss and mutations in the beta2m gene. Loss of HLA class I 
      expression is thus a frequent event in MAP carcinomas, similarly to MMR-deficient 
      colorectal tumours. The extensive mutagenic background of these tumours most 
      likely triggers a strong selective pressure, exerted by the immune system on the 
      tumour, which favours the outgrowth of tumour cell clones with an immune evasive 
      phenotype. Our data provide additional evidence for a link between DNA repair 
      deficiencies and altered HLA class I phenotypes in colorectal cancer.
FAU - de Miranda, Noel F C C
AU  - de Miranda NF
AD  - Department of Pathology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Nielsen, Maartje
AU  - Nielsen M
FAU - Pereira, Dina
AU  - Pereira D
FAU - van Puijenbroek, Marjo
AU  - van Puijenbroek M
FAU - Vasen, Hans F
AU  - Vasen HF
FAU - Hes, Frederik J
AU  - Hes FJ
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
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (TAP1 protein, human)
RN  - 0 (beta 2-Microglobulin)
RN  - 145892-13-3 (TAP2 protein, human)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (mutY adenine glycosylase)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 3
MH  - ATP-Binding Cassette Transporters/genetics
MH  - Adult
MH  - Antigen Presentation
MH  - Carcinoma/*genetics/immunology/pathology
MH  - Colorectal Neoplasms/*genetics/immunology/pathology
MH  - DNA Glycosylases/*genetics
MH  - DNA Repair
MH  - Gene Deletion
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Genes, MHC Class I
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Middle Aged
MH  - Mutation
MH  - Sequence Analysis, DNA
MH  - beta 2-Microglobulin/genetics
EDAT- 2009/05/23 09:00
MHDA- 2009/10/10 06:00
CRDT- 2009/05/23 09:00
PHST- 2009/05/23 09:00 [entrez]
PHST- 2009/05/23 09:00 [pubmed]
PHST- 2009/10/10 06:00 [medline]
AID - 10.1002/path.2569 [doi]
PST - ppublish
SO  - J Pathol. 2009 Sep;219(1):69-76. doi: 10.1002/path.2569.