Analysis of the Relationship Between EGFR Mutations and PD-L1, ALK, and ROS1 Alterations in Patients with Non- Small-Cell Lung Cancer: The Most Extensive Study Conducted in Iran.

Abstract

Objective: Lung cancer, the second most common type of cancer, is the leading cause of cancer-related mortality, with non-small-cell lung carcinoma (NSCLC) being the most prevalent subtype. The presence of EGFR mutations in NSCLC influences tumor behavior and treatment response. The prevalence of EGFR mutation in Iranian patients is limited. This study investigated the frequency of EGFR mutation and its association with PD-L1, ALK, and ROS1 expression in patients with NSCLC from Northwest Iran.

Material and methods: A retrospective analysis was conducted on 647 cases of NSCLC from April 2018 to August 2024 at Imam Reza Hospital in Tabriz, Iran. Histologic diagnoses were confirmed, and patient data were collected. EGFR mutation testing targeted exons 18-21 using Sanger sequencing and Real-Time PCR. ALK and ROS1 rearrangements were assessed using fluorescence in situ hybridization (FISH), while PD-L1 expression was evaluated through immunohistochemistry (IHC). The statistical analysis was performed using SPSS version 27.0.

Results: The cohort comprised 430 males and 217 females, with a median age of 62 years (IQR: 54-70). EGFR mutations were identified in 171 (26.4%) cases, more frequently in females (33.6% vs. 22.8%; p = 0.003). The most common mutation was exon 19 deletion (56.7%), followed by L858R (21.6%). No significant association was found between EGFR mutations and ALK (p = 0.126) or PD-L1 expressions ( p = 0.29). ROS1 mutations were not detected.

Conclusion: This study confirmed the mutual exclusivity of EGFR and ALK mutations and found no significant association with PD-L1. Comprehensive EGFR testing remains crucial to guide targeted therapies. Broader studies are needed to include diverse populations and additional clinical factors to improve personalized treatment.