EBUS-FNA cytologic-histologic correlation of PD-L1 immunohistochemistry in non–small cell lung cancer

Abstract

Immune checkpoint pathway markers induce immune tolerance to non-small cell lung cancer (NSCLC). Therapeutic antibodies targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have demonstrated efficacy in tumors expressing relatively high PD-L1 levels. Minimally invasive endobronchial ultrasound-guided fine needle aspiration allows patients with inoperable tumors or comorbidities to attain a confirmatory diagnosis. The aims of the present study were to determine whether PD-L1 testing is equivalent to cytology and biopsy or resection specimens at different tumor proportion score cutoffs and for different NSCLC subtypes. Data were retrospectively collected for patients with paired NSCLC cytology and surgical resection specimens from May 4, 2007 to May 4, 2017. The Food and Drug Administration-approved Dako PD-L1 immunohistochemistry 22C3 pharmDx kit was used to measure PD-L1 on paired cytology cell block and biopsy or resection specimens, and the PD-L1 tumor proportion scores were recorded. Statistical analysis of categorical and continuous variables was performed using SAS, version 9.4. A total of 53 paired cytology and resection samples (27 adenocarcinoma, 25 squamous cell carcinoma, and 1 unclassified) were analyzed. Supposing the resection specimen to reflect the true PD-L1 expression, the sensitivity, specificity, positive predictive value, negative predictive value, and overall agreement for the cytology method was 73.3%, 65.2%, 73.3%, 65.2%, and 69.8%, respectively. For high PD-L1 expression (≥50%), the cytology method demonstrated an overall agreement of 79.2%. The overall agreement between methods was 81.5% and 76% for cases of adenocarcinoma and squamous cell carcinoma, respectively. NSCLC cytology samples from endobronchial ultrasound-guided fine needle aspiration are suitable for PD-L1 testing, especially using a high PD-L1 expression cutoff of ≥50% and for adenocarcinoma.