Clinical Characters in Pre-invasive and Invasive Adenocarcinoma with Pulmonary Ground-glass Nodules

Purpose: With the increasing prevalence of pulmonary ground-glass nodules (GGNs) among younger population, its clinicopathologic performance, lung cancer-associated genetic mutation, and immune landscape features between pre-invasive adenocarcinoma and invasive adenocarcinoma (IAC) need to be get well known.Methods: We retrospectively reviewed basic clinical information, analyzed radiological characteristics, and then evaluated the status of mutational hotspots and tumor mutational burden by sequencing genome in tissue. Programmed death ligand 1 (PD-L1) expression was detected by immunohistochemistry staining. Results: Nodules vastly increased the probability of IAC when the diameter of GGNs was more than 1.15 mm or the consolidation-to-tumor ratio was at least 8.5%, with the latter predictor having a better diagnostic specificity. Tumors positive for exon 19 deletion and exon 21 L858R in EGFR mutation had a higher prevalence in IAC. However, there was no difference in PD-L1 expression. As expected, tumor mutational burden in IAC was higher, despite a low background mutational burden as a whole. Conclusions: GGNs should be pay high attention when several aggressive behaviors showed in radiology and inner solid components increased gradually, providing more evidence apt to a diagnosis of IAC. We found that GGNs of IAC performed early genomic alternations events during the slow growth carcinogenesis stage of GGNs, including the most common proto-oncogene EGFR activation, which mainly concentrates on IAC. Indolent GGNs at an early stage usually have negative PD-L1 expression.