The Association of Programmed Cell Death-Ligand 1 Expression with Early Evolution from Adenocarcinoma in Situ to Invasive Adenocarcinoma

Objectives: The role of programmed cell death‐ligand 1 (PD‐L1) pathway in early-stage lung adenocarcinoma is not clear. The aim of this study was to investigate the PD-L1 expression and its association with early-stage lung adenocarcinoma evolution from adenocarcinoma in situ (AIS) to invasive adenocarcinoma.Materials and methods: We evaluated PD-L1 expression in 1,123 consecutive surgically resected lung adenocarcinoma specimens of AIS, minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) of stage IA1-IA3. PD-L1 expression was defined based on the proportion of stained tumor cells (TPS) on tissue microarrays: <1% (negative), >1% (positive) and ≥ 50% (strongly positive). Correlations between PD-L1 expression and pathological stage, International Association for the Study of Lung Cancer (IASCL) adenocarcinoma grade, spread through air space (STAS), multiple primary lung cancer (MLPC) and driver oncogene (EGFR, KRAS, ALK, ROS1, BRAF and RET) alterations in lung adenocarcinoma were analyzed.Results: PD-L1 expression was almost negative in AIS or MIA. However, PD-L1 expression was positively increased with the emergering of invasiveness in lung adenocarcinoma. PD-L1 positive percentages in IA1-IA3 were 7.22%, 11.29% and 14.20%, respectively. PD-L1 strongly positive rates were 0.38%, 1.64% and 3.70% in IA1-3, respectively. PD-L1 expression was also negative in IASLC Grade 1 lung adenocarcinoma, however, PD-L1 expression was associated with poor pathological subtype and bad bio behavior, such as Grade 3 adenocarcinoma and STAS. PD-L1 expression was not associated with MPLC. In terms of driven genes, PD-L1 expression was not associated with EGFR mutation, but significantly related with KRAS, ROS-1 and ALK genetic alternation.Conclusion: PD-L1 expression was positively correlated with the emerging of invasiveness and poor pathological subtype of early-stage lung adenocarcinoma. PD-L1 pathway may be involved in the early evolution of lung adenocarcinoma from AIS to invasive adenocarcinoma.