High co-expression of PD-L1 and HIF-1α correlates with tumour necrosis in pulmonary pleomorphic carcinoma
Journal
European Journal of Cancer
Journal Volume
60
Pages
125-135
Date Issued
2016
Abstract
Background 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. Materials and methods 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. Results 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. Conclusions 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. ? 2016 Elsevier Ltd. All rights reserved.
Other Subjects
anaplastic lymphoma kinase; B Raf kinase; epidermal growth factor receptor; hypoxia inducible factor 1alpha; K ras protein; paraffin; phosphatidylinositol 3 kinase; phosphoinositide 3 kinase catalytic alpha; programmed death 1 ligand 1; protein tyrosine kinase; ROS1 protein; telomerase reverse transcriptase; unclassified drug; CD274 protein, human; hypoxia inducible factor 1alpha; programmed death 1 ligand 1; tumor protein; adult; aged; Article; cancer patient; correlational study; East Asian; female; gene mutation; gene overexpression; human; human tissue; investigative procedures; lung carcinoma; major clinical study; male; malignant neoplastic disease; non small cell lung cancer; outcome assessment; overall survival; priority journal; protein expression; pulmonary pleomorphic carcinoma; tumor cell; tumor necrosis; genetics; Kaplan Meier method; lung tumor; metabolism; metastasis; middle aged; mortality; mutation; necrosis; pathology; very elderly; young adult; Adult; Aged; Aged, 80 and over; Antigens, CD274; Carcinoma, Non-Small-Cell Lung; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Necrosis; Neoplasm Metastasis; Neoplasm Proteins; Young Adult
Publisher
Elsevier Ltd
Type
journal article