Abstract
Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide
Programmed Death-Ligand 1 (PD-L1) expression by neoplastic cells of bronchial dysplasia has been suggested by recently published reports
PD-L1 mRNA levels were higher than control and might be enhanced by LKB1 (Liver Kinase B1)
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide. For bronchial and lung neoplasms, three pre-invasive lesions are recognized: (1) bronchial dysplasia for lung squamous cell carcinoma, (2) atypical adenomatous hyperplasia for lung adenocarcinoma and (3) diffuse idiopathic pulmonary neuroendocrine hyperplasia for carcinoids. Bronchial dysplasia can arise from any part of the bronchial tree, predominantly in tobacco smokers. Bronchial dysplasia is graded as mild, moderate or high grade dysplasia with a higher risk of progression to invasive squamous carcinoma for patients with high grade dysplasia. Endoscopic imaging with fluorescence endoscopy has enhanced the detection and location of bronchial dysplasia, being mandatory for patients’ management.
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