High co-expression of PD-L1 and HIF-1α correlates with tumour necrosis in pulmonary pleomorphic carcinoma.
Pulmonary pleomorphic carcinomas (PPCs) are uncommon malignant tumours characterised by an aggressive clinical course and poor survival. These neoplasms frequently exhibit marked confluent necrosis, in which hypoxia levels are extremely high, causing low responsiveness to chemotherapy and conferring basic resistance to anti-cancer drugs. Programmed death ligand 1 (PD-L1)-mediated immune escape may be an underlying source of resistance and a suitable target for specific therapy, but its role in PPCs is unclear.



In total, 122 PPCs were investigated. Paraffin-embedded tumour sections were stained with PD-L1 and hypoxia-inducible factor-1α (HIF-1α) antibodies. Overexpression was denoted by moderate-to-strong PD-L1 membrane staining in ≥5% of tumour cells and HIF-1α nuclear staining in ≥10% of tumour cells. The presence of driver mutations in the epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), telomerase reverse harscriptase gene (TERT), phosphoinositide 3-kinase catalytic alpha (PIK3CA), anaplastic lymphoma kinase (ALK), and ROS1 (ROS1 proto-oncogene receptor tyrosine kinase) genes were examined.



The overall frequencies of PD-L1 and HIF-1α overexpression and EGFR mutation were 70.5, 75.4, and 22.1%, respectively. High PD-L1 expression was significantly correlated with that of HIF-1α (p < 0.001) and tumour necrosis (p < 0.001). HIF-1α expression was associated with EGFR mutation (p = 0.015). Advanced stage and high PD-L1 expression were two independent risks for poor overall survival.



High PD-L1 and HIF-1α co-expression was observed in PPCs compared with their expression in conventional non-small-cell lung carcinoma. The aggressive behaviour of PPC could be partially related to PD-L1-mediated immune escape and intratumoural hypoxia. High PD-L1 expression correlates with poor prognosis and may provide a rationale for the use of targeted immunotherapy in this subtype of high-grade PPC.
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Yih-Leong
YL
Chang
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Ching-Yao
CY
Yang
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Mong-Wei
MW
Lin
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan. Electronic address: ipohdamu@gmail.com.
Chen-Tu
CT
Wu
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan; National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan.
Pan-Chyr
PC
Yang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009336:Necrosis; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics; D000090063:Proto-Oncogene Mas; D055815:Young Adult
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas
Hypoxia-inducible factor 1-α; Immunotherapy; Pleomorphic carcinoma; Programmed cell-death ligand 1