Association of histologic subtypes with genetic alteration and PD‑L1 expression in pulmonary adenocarcinoma

Abstract

Genetic alteration and programmed death-ligand 1 (PD-L1) expression have been revealed to be associated with various subtypes of pulmonary adenocarcinoma (ADC). The present study aimed to explore the association between histological subtypes and genetic alterations and PD-L1 expression. A total of 375 cases of pulmonary ADC were included. Genetic alterations were determined using next generation sequencing (NGS) in 136 cases. PD-L1 expression was detected by immunohistochemistry (based on clone 22C3) in the remaining 239 cases. Mutations in the epidermal growth factor receptor gene (EGFR) were detected in 76 (55.8%) cases associated with the papillary subtype (P=0.038). Mutations in the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) were present in 46 (33.8%) cases associated with the lepidic subtype (P<0.001) and mucinous ADC (P=0.037). PD-L1 expression was identified in 63 (26.4%) cases associated with the solid subtype (P<0.001). In conclusion, the present study demonstrated that EGFR and KRAS mutations, alongside PD-L1 protein expression are significantly associated with specific subtypes of pulmonary ADC. These results should aid our ability to accurately select appropriate areas of the heterogeneous tumor for molecular testing methods and to predict patient outcomes and prognosis.

Clinicopathologic Features and Molecular Biomarkers as Predictors of Epidermal Growth Factor Receptor Gene Mutation in Non-Small Cell Lung Cancer Patients

“…Girard et al [ 14 ] revealed that in both East Asia and non-Asia, EGFR mutations were common in papillary predominant adenocarcinoma (PPA) (30%) but rare in APA or solid predominant adenocarcinoma with mucin production (SPA). A recent study [ 30 ] also pointed out that PPA was associated with a high rate of EGFR mutations (23.7% vs. 76.3, p = 0.038). Shim et al [ 13 ] analyzed 107 ADC patients and found the mutation in micropapillary predominant adenocarcinoma (MPA) was more common than that in other histological subtypes (83.3% vs. 46.3%, p = 0.02).…”

Programmed Death Ligand 1 Expression in Lung Adenocarcinoma: An Analysis of the Histomorphological Features

“…wherein the authors concluded that solid predominant adenocarcinoma was constantly related with high PD-L1 positivity. [ 9 ] The results of the research studies conducted by Driver et al . and Pan et al .…”

“…[ 8 ] Programmed death ligand-1 (PD-L1) positivity in adenocarcinoma phenotype is related with advanced disease and lymph node involvement. [ 9 ] A detailed analysis of the histomorphological features may define the presence of specific pattern or feature in the phenotype with PD-L1 expression. The study was undertaken with the objectives to analyze the detailed histomorphological features of adenocarcinoma lung with PD-L1 expression in tumor cells and to compare histomorphological features with PD-L1 negative group.…”

PPIB/Cyclophilin B expression associates with tumor progression and unfavorable survival in patients with pulmonary adenocarcinoma

“…Adenocarcinoma (ADC), the most common histological type, and squamous cell carcinoma, another common subtype, are the two major subtypes of NSCLCs, accounting for more than 85% of the cases [3]. As they exhibit distinct characteristics, including differences in the origin of tumor cells, location, specific biomarkers, and oncogenic drivers [4], the histopathologic subtype has become a crucial factor in NSCLC patient survival and in guiding their therapeutic plan [5,6]. Additionally, the Ki-67 labeling index is a well-established histological marker for predicting the survival of patients with NSCLC [7].…”