title: PD-L1 is highly expressed in lung lymphoepithelioma-like carcinoma: A potential rationale for immunotherapy.
abstract: OBJECTIVE
  Programmed cell death-ligand 1 (PD-L1) and driver mutations are found in non-small cell lung cancers (NSCLCs) and may be suitable targets for specific therapies, but their roles in lymphoepithelioma-like carcinoma (LELC) of the lung are unclear.
  
  
  METHODS
  Sixty-six patients with pulmonary LELCs were investigated. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Tumors with moderate-to-strong membrane staining in ≥5% of tumor cells were positive for PD-L1 overexpression. The presence of driver mutations in the genes for epidermal growth factor receptor (EGFR), KRAS, and BRAF were examined by direct sequencing. Anaplastic lymphoma kinase (ALK) and ROS1 levels were determined by immunohistochemistry. Correlations of PD-L1 expression and driver mutations with clinicopathologic parameters were analyzed.
  
  
  RESULTS
  The overall frequency of PD-L1 overexpression and EGFR mutation was 75.8% and 12.1%, respectively. No KRAS, BRAF, ALK or ROS1 aberrations could be detected. PD-L1 expression was not associated with driver mutations. Multivariate analysis revealed that smoking and advanced stage were independent risk factors for poor overall survival, whereas PD-L1 positivity was not significantly associated with patient outcome.
  
  
  CONCLUSIONS
  There are high PD-L1 expression and infrequent driver mutations in LELCs compared with conventional NSCLCs. The high expression of PD-L1 in EBV and inflammation associated LELC may provide a rationale for immunotherapy in this subtype of lung cancer.
authors: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Yih-Leong
authors: YL
authors: Chang
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Ching-Yao
authors: CY
authors: Yang
authors: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Mong-Wei
authors: MW
authors: Lin
authors: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: ipohdamu@gmail.com.
authors: Chen-Tu
authors: CT
authors: Wu
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan; National Taiwan University, Taipei, Taiwan.
authors: Pan-Chyr
authors: PC
authors: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins
keywords: Driver mutation; EGFR; Immunotherapy; KRAS; Lung cancer; PD-L1; Pulmonary lymphoepithelioma-like carcinoma