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JPTM > Ahead-of Print

doi: https://doi.org/10.4132/jptm.2018.12.26    [Epub ahead of print]
Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Co-expression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung
Yeon Bi Han1, Hyun Jung Kwon1, Soo Young Park1, Eun-Sun Kim1, Hyojin Kim1, Jin-Haeng Chung1,2
1Department of Pathology Seoul National University Bundang Hospital, Seongnam, Korea
2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
Corresponding Author: Jin-Haeng Chung ,Tel: +82-31-787-7713, Fax: +82-31-787-4012, Email: chungjh@snu.ac.kr
Received: July 20, 2018;  Revised: December 1, 2018  Accepted: December 26, 2018.  Published online: January 14, 2019.
ABSTRACT

Background:
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods:
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results:
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p=0.033, p=0.007 and p=0.012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p<0.001, p=0.002 and p=0.032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p=0.001). Multivariate analysis revealed that co-expression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p<0.001, Hazard ratio=6.106 with 95% confidence interval 2.260-16.501)
Conclusion:
Lung adenocarcinoma with co-expression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite of HLA expression.
Key Words: Human leukocyte antigen class I; Programmed cell death-ligand 1; Non-small cell lung cancer; Immunohistochemistry