Heterogeneity of PD-L1 Expression Among the Different Histological Components and Metastatic Lymph Nodes in Patients With Resected Lung Adenosquamous Carcinoma

Introduction: Programmed death-ligand 1 (PD-L1) expression using immunohistochemistry is approved by the US Food and Drug Administration to guide treatment with anti-programmed death-1/PD-L1 monoantibodies. However, intratumoral heterogeneity of PD-L1 expression and the accordance between primary and metastatic lesions remains unresolved.

Materials and methods: PD-L1 expression was evaluated in tumor cells and tumor-infiltrating lymphocytes (TILs) of surgically resected lung adenosquamous carcinoma. Discrepancy of PD-L1 expression and cluster of differentiation 8-positive TILs of different histologic components was investigated. PD-L1 expression was also compared between primary tumor and nodal metastases.

Results: The study included a total of 72 lung adenosquamous carcinomas. Fifteen patients (20.8%) and 25 patients (34.7%) were positive for PD-L1 expression in adenomatous and squamous components respectively, with a cutoff value of 5%. We found that 57.8% of cases showed consistent PD-L1 expression in tumor cells in the different histological components at a cutoff of 1%, and 48.1% of cases were likewise consistent at a cutoff of 5%. In paired squamous components of metastatic nodes and primary lesions, 90% and 80% of cases of PD-L1 expression were consistent, at cutoffs of 1% and 5%, respectively. For the adenomatous component of tumor/metastasis pairs, 77.8% of cases at the 1% cutoff and 74.1% of cases at the 5% cutoff were consistent, partially attributed to the difference of predominant histologic patterns.

Conclusion: PD-L1 expression showed discrepancy in different histological components within a tumor and consistency in paired histological type between tumor and metastases. Different pathological features might contribute to the heterogeneous PD-L1 expression in patients with non-small-cell lung cancer.