Background: Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features.Patients and Methods: PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival.Results: A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23–94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PD-L1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominant-papillary pattern, and 68.7% of patients with predominant-solid pattern (p = 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS.Conclusion: According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.

, 53 patients were females (73%), and 68 (94.5%) had common mutations. Twenty-two (30.6%) samples with EGFR activating mutations were identified as having EGFR amplification. EGFR amplification was more frequent in patients with exon 19 deletion (p¼0.05) and in those with better performance status (p¼0.01). Patients with EGFR gene amplification had a significantly longer PFS than those without [(28.5 months, 95%CI 22.3-34.6) vs. (11.0 months, 95%CI 8.23-16.7); p¼0.002] as well as better OS [(EGFR amplified 37.8 months, 95%CI 30.9-44.7) vs. (EGFR non-amplified 27.1 months, 95%CI 12.8-41.3); p¼0.009]. EGFR amplification significantly influenced the response to erlotinib (p¼0.0001). Conclusion: In the Hispanic population studied, EGFR amplification was present in one third of the patients with lung ADC harboring EGFR activating mutations. EGFR gene copy number detected by FISH, and sensitizing EGFR mutations are biomarkers associated with better OS, PFS, and response to EGFR-TKI therapy in patients with advanced NSCLC. EGFR copy number could serve as a predictive marker for the identification of patients with NSCLC who will most benefit from EGFR-TKI treatment.