CTNNB1 Mutations in Non-small Cell Lung Cancer: Clinicopathological Characteristics of a Small Cohort

Background/Aim: Mutations in β-catenin gene (CTNNB1) are very rare in non-small cell lung cancer (NSCLC) and frequently coexist with epidermal growth factor receptor (EGFR) mutations. This study evaluated the clinicopathological characteristics and treatments outcomes of 14 patients harboring CTNNB1 mutations. Patients and Methods: A total of 266 NSCLC samples underwent Next Generation Sequencing (NGS) from October 2022 to December 2024. Patients carrying mutation in exon 3 of CTNNB1 were compared to a control group of CTNNB1-wild type/EGFR-mutated patients. We analyzed the clinicopathological characteristics and the outcomes of the two groups of patients. Results: CTNNB1 mutations were identified in 5.3% (14/266) of the cohort. Only 28.6% of these patients had an exclusive CTNNB1 mutation, while 71.4% exhibited concomitant mutations, mainly in EGFR gene (42.6%). Patients with CTNNB1 mutations were diagnosed at a significantly higher median age (p=0.013) and showed lower PDL1 expression (p=0.036) compared to control group. The CTNNB1 mutated patients achieved a median overall survival (OS) of 29 months vs. 23 months in the control group. Interestingly, patients with concurrent EGFR and CTNNB1 mutations reached a median OS of 35.5 months; however, this trend did not reach statistical significance due to the small sample size. Conclusion: CTNNB1 mutations in NSCLC are associated with older age at diagnosis, lower PD-L1 expression and potentially favorable survival outcomes, particularly when appearing alongside EGFR mutations.