Abstract
BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression by the 22C3 pharmDx companion assay has been validated in surgical specimens to support pembrolizumab treatment decisions for patients with non-small cell lung carcinoma (NSCLC). The aims of this study were 1) to assess the adequacy of cytologic specimens for PD-L1 evaluation and 2) to explore correlations of PD-L1 expression with clinicopathologic and molecular features. METHODS: The study cohort included 100 cytology specimens (fluid [n = 28] and fine-needle aspiration [n = 72]) and 165 surgical specimens (biopsy [n = 138] and resection [n = 27]). The PD-L1 immunohistochemistry 22C3 assay and staining assessment were performed according to the manufacturer's instructions. PD-L1 expression was correlated with patients' demographics, pathologic characteristics, and molecular alterations. RESULTS: One hundred forty-two specimens (53.6%) were positive for PD-L1 expression (≥1%). No statistically significant difference in PD-L1 expression was identified between cytologic (56.0%) and surgical specimens (52.1%). Seventy-four of 190 tested cases (38.9%) had genetic alterations. PD-L1 positivity was significantly more prevalent in cases with genetic alterations than in cases without genetic alterations. Furthermore, both PD-L1 positivity and high PD-L1 expression (≥50%) had statistically significant associations with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. PD-L1 expression had no significant association with histologic phenotypes or other clinicopathologic features. CONCLUSIONS: The data indicate that cytologic specimens are comparable to surgical specimens for PD-L1 evaluation. The association of PD-L1 expression with KRAS mutations may have clinical relevance in selecting patients with NSCLC for immunotherapy.