J Pathol Transl Med.  2019 Mar;53(2):86-93. 10.4132/jptm.2018.12.26.

Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung

• Han YB
• Kwon HJ
• Park SY
• Kim ES
• Kim H
• Chung JH

• KMID: 2465447
• DOI: http://doi.org/10.4132/jptm.2018.12.26

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 = .033, p = .007, and p = .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 < .001, p = .002, and p = .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 = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
CONCLUSIONS
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.

Keyword

Human leukocyte antigen class I; Programmed cell death-ligand 1; Carcinoma, non-small cell lung; Immunohistochemistry

MeSH Terms

Adenocarcinoma*
Carcinoma, Non-Small-Cell Lung
Humans*
Immunohistochemistry
Leukocytes*
Lung*
Multivariate Analysis
Neoplasm Metastasis
Prognosis

Figure

• 

  Fig. 1. Human leukocyte antigen (HLA) class I (A–C) and programmed death-ligand 1 (PD-L1) (D–E) expression in lung adenocarcinoma. (A) Strongly positive (“retained”) staining of HLA class I in tumor cells. (B) Weakly positive staining of HLA class I. (C) Negative staining of HLA class I. (D) ≥50% positive staining of PD-L1 in tumor cells. (E) 1%–49% positive staining of PD-L1. (F) <1% staining of PD-L1.

• 

  Fig. 2. Association of human leukocyte antigen (HLA) class I antigen and programmed death-ligand 1 (PD-L1) expression in lung adenocarcinoma (ADC) lesions with overall survival in patients. (A) Overall survival curves of patients with lung ADC according to their HLA class I expression. (B) Overall survival curves according to PD-L1 expression status classified by the percentage of tumor cells expressing PD-L1 at the cutoff value of 1%. (C) Overall survival in patients classified by expression of HLA class I and PD-L1. Patients were divided into four groups: HLA class I (–)/PD-L1 (–), HLA class I (–)/PD-L1 (+), HLA class I (+)/PD-L1 (–), HLA class I (+)/PD-L1 (+).

• 

  Fig. 3. Overall survival according to programmed death-ligand 1 (PD-L1) expression after stratification by human leukocyte antigen (HLA) class I expression status. (A) Overall survival curves according to PD-L1 expression status (1% cutoff) among “retained” HLA class I cases. (B) Overall survival curves according to PD-L1 expression status (1% cutoff) among “reduced” HLA class I cases.

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