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01-11-2019 | Epstein-Barr Virus | Original Article

Clinicopathologic significance of human leukocyte antigen class I expression in patients with stage II and III gastric cancer

Authors: Yujun Park, Jiwon Koh, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee

Published in: Cancer Immunology, Immunotherapy | Issue 11/2019

Abstract

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 (β2M) 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, β2M, 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 β2M 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 β2M 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 β2M 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 β2M 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.

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Title: Clinicopathologic significance of human leukocyte antigen class I expression in patients with stage II and III gastric cancer
Authors: Yujun Park
Jiwon Koh
Yoonjin Kwak
Sang-Hoon Ahn
Do Joong Park
Hyung-Ho Kim
Woo Ho Kim
Hye Seung Lee
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Epstein-Barr Virus
Gastric Cancer
Gastric Cancer
Biomarkers
Published in: Cancer Immunology, Immunotherapy / Issue 11/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02410-z

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