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J Thorac Dis. 2018 Jul;10(7):4433-4444. doi: 10.21037/jtd.2018.06.167.

Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma.

Hsieh CC1,2, Hsu HS1,3, Li AF4,5, Chen YJ2,6,7.

Author information

1
Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei.
2
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei.
3
Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei.
4
Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei.
5
School of Medicine, National Yang-Ming University, Taipei.
6
Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei.
7
Department of Pediatrics, Renai Branch, Taipei City Hospital, Taipei.

Abstract

Background:

Even with the advance of diagnosis and the treatment, the 5-year survival rate for esophageal cancer patients is still poor. The checkpoint protein inhibition provides another choice to improve the survival. The expression of the programmed death ligand-1 (PD-L1) was reported but the clinical relevance remained inconsistent in esophageal cancer. Besides, there were few references about the other ligand, programed death ligand-2 (PD-L2). In this study, we evaluated the expressions of PD-L1 and PD-L2 in patients with esophageal squamous cell carcinoma (ESCC) and assessed their clinical relevance.

Methods:

From 1996 to 2011, 150 patients undergone complete surgical resection for ESCC were enrolled. Clinical data were recorded. Expression of PD-L1 and PD-L2 on cytoplasm in paraffin embedded tumor samples were analyzed by immunohistochemistry staining and scored with a semi-quantitative method.

Results:

Of the patients, 96 (64.0%) patients had PD-L1 overexpression and 63 (42.0%) had PD-L2 overexpression. There was a correlation between the expression of PD-L1 and PD-L2 (P<0.001). Patients without overexpression of PD-L1, pathological T1-2 and N0 status, pathological stage I-II and no post-operative adjuvant treatment had a better disease free survival (DFS). In multivariate analysis, PD-L1 expression and pathological stage were the independent prognostic factors for DFS. The expression of PD-L2 did not influence the DFS. Although not statistically significant, patients without overexpression of PD-L1 and PD-L2 seem to have a better overall survival (OS).

Conclusions:

The overexpression of PD-L1 on cytoplasm, not PD-L2, is an independent prognostic factor for DFS in patients with ESCC undergone esophagectomy. However, there is a trend which suggested that patients without overexpression of PD-L1 and PD-L2 had a better OS.

KEYWORDS:

Programmed death ligand-1 (PD-L1); cytoplasm; esophageal squamous cell carcinoma (ESCC); overexpression; programed death ligand-2 (PD-L2); survival

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

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