PMID- 31620857
OWN - NLM
STAT- MEDLINE
DCOM- 20191127
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 68
IP  - 11
DP  - 2019 Nov
TI  - Clinicopathologic significance of human leukocyte antigen class I expression in 
      patients with stage II and III gastric cancer.
PG  - 1779-1790
LID - 10.1007/s00262-019-02410-z [doi]
AB  - Human leukocyte antigen class I (HLA I) molecules composed of alpha (heavy) 
      chain, including HLA-A, -B, or -C encoded by HLA genes, and beta-2-microglobulin 
      (beta2M) are membrane proteins on all nucleated cells that display peptide antigens 
      for recognition by CD8-positive cytotoxic T cells. Here, we examined the 
      clinicopathologic signification of HLA I expression in patients with gastric 
      cancer (GC). Immunohistochemistry was performed to detect HLA A/B/C, beta2M, CD8, 
      p53, and programmed death-ligand 1 (PD-L1) in the center and invasive margin of 
      the tumor in 395 stage II and III GCs using tissue array method. Additionally, 
      Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status 
      were investigated. Negative expression of HLA A/B/C and beta2M was observed in 258 
      (65.3%) and 235 (59.5%) of 395 stage II and III GCs, respectively. Negative HLA I 
      expression was significantly associated with aggressive clinicopathologic 
      features. Furthermore, negative expression of HLA A/B/C and beta2M was inversely 
      correlated with CD8-positive cytotoxic T cell infiltration, EBV-positivity, and 
      PD-L1 expression (all p < 0.001). Patients with HLA A/B/C-negative GC had worse 
      overall survival (OS) (p = 0.019) and combined analysis with both HLA A/B/C and 
      beta2M expression status significantly predicted OS in univariate (p = 0.004) and 
      multivariate survival analysis (p = 0.016). Negative expression of HLA A/B/C and 
      beta2M was frequently observed in stage II and III GCs, particularly with the 
      aggressive clinicopathologic features, and correlated with an unfavorable 
      prognosis and host immune response status. These findings contribute to further 
      development of immunotherapy.
FAU - Park, Yujun
AU  - Park Y
AD  - Department of Pathology, Seoul National University Bundang Hospital, Gumi-ro 173, 
      82 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-do, 13620, Republic of Korea.
AD  - Department of Pathology, Seoul National University College of Medicine, 103 
      Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
FAU - Koh, Jiwon
AU  - Koh J
AD  - Department of Pathology, Seoul National University Hospital, 100 Daehak-ro, 
      Jongno-gu, Seoul, Republic of Korea.
FAU - Kwak, Yoonjin
AU  - Kwak Y
AD  - Department of Pathology, Seoul National University Hospital, 100 Daehak-ro, 
      Jongno-gu, Seoul, Republic of Korea.
FAU - Ahn, Sang-Hoon
AU  - Ahn SH
AD  - Department of Surgery, Seoul National University Bundang Hospital, Gumi-ro 173, 
      82 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-do, Republic of Korea.
FAU - Park, Do Joong
AU  - Park DJ
AD  - Department of Surgery, Seoul National University Bundang Hospital, Gumi-ro 173, 
      82 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-do, Republic of Korea.
FAU - Kim, Hyung-Ho
AU  - Kim HH
AD  - Department of Surgery, Seoul National University Bundang Hospital, Gumi-ro 173, 
      82 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-do, Republic of Korea.
FAU - Kim, Woo Ho
AU  - Kim WH
AD  - Department of Pathology, Seoul National University College of Medicine, 103 
      Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
AD  - Department of Pathology, Seoul National University Hospital, 100 Daehak-ro, 
      Jongno-gu, Seoul, Republic of Korea.
FAU - Lee, Hye Seung
AU  - Lee HS
AUID- ORCID: 0000-0002-1667-7986
AD  - Department of Pathology, Seoul National University Bundang Hospital, Gumi-ro 173, 
      82 Beon-gil, Bundang-gu, Seongnam-Si, Gyeonggi-do, 13620, Republic of Korea. 
      hye2@snu.ac.kr.
AD  - Department of Pathology, Seoul National University College of Medicine, 103 
      Daehak-ro, Jongno-gu, Seoul, Republic of Korea. hye2@snu.ac.kr.
LA  - eng
GR  - NRF-2016R1D1A1B03931744/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20191016
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CD274 protein, human)
RN  - 0 (HLA Antigens)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B7-H1 Antigen/immunology/metabolism
MH  - Biomarkers, Tumor/immunology/*metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - HLA Antigens/immunology/*metabolism
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Male
MH  - Microsatellite Instability
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Stomach Neoplasms/immunology/metabolism/*pathology/surgery
MH  - Tumor Microenvironment/*immunology
MH  - Young Adult
MH  - beta 2-Microglobulin/immunology/metabolism
PMC - PMC11028069
OTO - NOTNLM
OT  - Beta-2-microglobulin
OT  - Biomarkers
OT  - Gastric cancer
OT  - Human leukocyte antigen
OT  - Programmed death-ligand 1
COIS- The authors report no conflict of interest.
EDAT- 2019/10/18 06:00
MHDA- 2019/11/28 06:00
PMCR- 2019/10/16
CRDT- 2019/10/18 06:00
PHST- 2018/11/25 00:00 [received]
PHST- 2019/10/05 00:00 [accepted]
PHST- 2019/10/18 06:00 [pubmed]
PHST- 2019/11/28 06:00 [medline]
PHST- 2019/10/18 06:00 [entrez]
PHST- 2019/10/16 00:00 [pmc-release]
AID - 10.1007/s00262-019-02410-z [pii]
AID - 2410 [pii]
AID - 10.1007/s00262-019-02410-z [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2019 Nov;68(11):1779-1790. doi: 
      10.1007/s00262-019-02410-z. Epub 2019 Oct 16.