PMID- 23401227
OWN - NLM
STAT- MEDLINE
DCOM- 20130927
LR  - 20230413
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 19
IP  - 7
DP  - 2013 Apr 1
TI  - LOH in the HLA class I region at 6p21 is associated with shorter survival in 
      newly diagnosed adult glioblastoma.
PG  - 1816-26
LID - 10.1158/1078-0432.CCR-12-2861 [doi]
AB  - PURPOSE: Glioblastoma (GBM) shows downregulated expression of human leukocyte 
      antigen (HLA) class I, thereby escaping from cytotoxic T cells and limiting the 
      efficacy of immunotherapy. Loss of heterozygosity (LOH) of HLA class I (6p21) 
      and/or beta-2 microglobulin (B2m) (15q21) regions represents irreversible 
      downregulation. In this study, we examined the prevalence of these LOH events and 
      their relations with overall survival in GBM. EXPERIMENTAL DESIGN: In a 
      cross-sectional analysis on 60 adult patients with GBM, DNA from formalin-fixed, 
      paraffin-embedded specimens were evaluated for 10 microsatellite regions of HLA 
      class I, B2m, HLA class II, HLA class III, and 6q by PCR as well as 
      immunohistochemical evaluation of HLA class I expression and CD8(+) T-cell 
      infiltration. RESULTS: LOH in HLA class I, B2m, HLA class II, HLA class III, and 
      6q regions was present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative 
      cases, respectively. LOH of HLA class I was associated with shorter overall 
      survival (HR = 4.89, P = 0.0078). HLA class I was downregulated in 22% to 43% of 
      cases based on immunohistochemistry. Cases that displayed negative staining were 
      significantly younger. HLA class I expression correlated with intratumoral CD8(+) 
      T-cell infiltration. CONCLUSION: LOH in the HLA class I region is frequent in 
      adult GBMs. The association of shorter survival with LOH in this region suggests 
      a crucial role for these genes in immunosurveillance.
CI  - (c)2013 AACR.
FAU - Yeung, Jacky T
AU  - Yeung JT
AD  - Department of Neurological Surgery, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA, USA.
FAU - Hamilton, Ronald L
AU  - Hamilton RL
FAU - Ohnishi, Koji
AU  - Ohnishi K
FAU - Ikeura, Maki
AU  - Ikeura M
FAU - Potter, Douglas M
AU  - Potter DM
FAU - Nikiforova, Marina N
AU  - Nikiforova MN
FAU - Ferrone, Soldano
AU  - Ferrone S
FAU - Jakacki, Regina I
AU  - Jakacki RI
FAU - Pollack, Ian F
AU  - Pollack IF
FAU - Okada, Hideho
AU  - Okada H
LA  - eng
GR  - 1P01 CA132714/CA/NCI NIH HHS/United States
GR  - 2R01 NS055140/NS/NINDS NIH HHS/United States
GR  - P01 CA132714/CA/NCI NIH HHS/United States
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - R01 NS055140/NS/NINDS NIH HHS/United States
GR  - P30CA047904/CA/NCI NIH HHS/United States
GR  - P01 NS040923/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130211
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD8-Positive T-Lymphocytes/pathology
MH  - Chromosomes, Human, Pair 15
MH  - *Chromosomes, Human, Pair 6
MH  - Cluster Analysis
MH  - Female
MH  - Glioblastoma/*genetics/metabolism/*mortality
MH  - Histocompatibility Antigens Class I/*genetics/metabolism
MH  - Humans
MH  - *Loss of Heterozygosity
MH  - Lymphocytes, Tumor-Infiltrating/pathology
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Prognosis
PMC - PMC3618546
MID - NIHMS444909
EDAT- 2013/02/13 06:00
MHDA- 2013/09/28 06:00
PMCR- 2014/04/01
CRDT- 2013/02/13 06:00
PHST- 2013/02/13 06:00 [entrez]
PHST- 2013/02/13 06:00 [pubmed]
PHST- 2013/09/28 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 1078-0432.CCR-12-2861 [pii]
AID - 10.1158/1078-0432.CCR-12-2861 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2013 Apr 1;19(7):1816-26. doi: 10.1158/1078-0432.CCR-12-2861. 
      Epub 2013 Feb 11.