PMID- 22287095
OWN - NLM
STAT- MEDLINE
DCOM- 20121031
LR  - 20161125
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 131
IP  - 8
DP  - 2012 Oct 15
TI  - Loss of HLA class I and mismatch repair protein expression in sporadic 
      endometrioid endometrial carcinomas.
PG  - 1828-36
LID - 10.1002/ijc.27449 [doi]
AB  - Tumor cells can escape from cytotoxic T-cell responses by downregulation of human 
      leukocyte antigen (HLA) class I molecules expressed at the cell surface which has 
      been associated with a deficient mismatch repair (MMR) system in colorectal 
      carcinomas. Our study investigated the association between expression of MMR 
      proteins and HLA class I in sporadic endometrioid endometrial carcinomas (EC). In 
      a consecutively selected cohort of 486 EC patients, MMR proteins (MLH1, MSH2 and 
      MSH6) and HLA class I (HLA-A, -B, -C or beta(2) m) were investigated by 
      immunohistochemistry. Expression levels of MMR proteins and HLA class I were 
      compared between low-grade and high-grade ECs. HLA class I expression was 
      compared between tumors with loss (negative immunostaining of >/=1 MMR protein) and 
      expression of MMR proteins. Associations between previously determined numbers of 
      intratumoral CD8(+) T-lymphocytes and expression of MMR proteins and HLA class I 
      and the influence on survival was determined. ECs with loss of MMR protein 
      expression (33.5%) more frequently have loss of HLA-B/C (37.3%), compared to ECs 
      with MMR protein expression (25.5%, p = 0.007). Patients with loss of MMR 
      proteins have a worse disease-specific survival compared to patients with 
      expression (p = 0.039). CD8(+) T-lymphocytes have a positive influence on 
      disease-free and disease-specific survival in the total EC cohort but not in 
      patients with loss of MMR protein expression. In conclusion, our results indicate 
      that loss of MMR protein expression is related to selective downregulation of HLA 
      class I which contributes to immune escape in EC with an abnormal MMR system.
CI  - Copyright (c) 2012 UICC.
FAU - de Jong, Renske A
AU  - de Jong RA
AD  - Department of Gynecologic Oncology, University of Groningen, University Medical 
      Center Groningen, Groningen, The Netherlands.
FAU - Boerma, Annemarie
AU  - Boerma A
FAU - Boezen, H Marike
AU  - Boezen HM
FAU - Mourits, Marian J E
AU  - Mourits MJ
FAU - Hollema, Harry
AU  - Hollema H
FAU - Nijman, Hans W
AU  - Nijman HW
LA  - eng
PT  - Journal Article
DEP - 20120309
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (G-T mismatch-binding protein)
RN  - 0 (MLH1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - EC 3.6.1.3 (MSH2 protein, human)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
RN  - EC 3.6.1.3 (MutS Homolog 2 Protein)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Aged
MH  - Biomarkers, Tumor/*metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Endometrial Neoplasms/immunology/*metabolism/mortality
MH  - Female
MH  - *Genes, MHC Class I
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lymphocytes, Tumor-Infiltrating/immunology/metabolism/pathology
MH  - Middle Aged
MH  - MutL Protein Homolog 1
MH  - MutS Homolog 2 Protein/*metabolism
MH  - Neoplasm Grading
MH  - Nuclear Proteins/*metabolism
MH  - Prognosis
MH  - Survival Rate
EDAT- 2012/01/31 06:00
MHDA- 2012/11/01 06:00
CRDT- 2012/01/31 06:00
PHST- 2011/06/19 00:00 [received]
PHST- 2012/01/03 00:00 [accepted]
PHST- 2012/01/31 06:00 [entrez]
PHST- 2012/01/31 06:00 [pubmed]
PHST- 2012/11/01 06:00 [medline]
AID - 10.1002/ijc.27449 [doi]
PST - ppublish
SO  - Int J Cancer. 2012 Oct 15;131(8):1828-36. doi: 10.1002/ijc.27449. Epub 2012 Mar 
      9.