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

<h3>Background/Aim:</h3> Mutations in β-catenin gene (<i>CTNNB1</i>) are very rare in non-small cell lung cancer (NSCLC) and frequently coexist with epidermal growth factor receptor (<i>EGFR</i>) mutations. This study evaluated the clinicopathological characteristics and treatments outcomes of 14 patients harboring <i>CTNNB1</i> mutations. <h3>Patients and Methods:</h3> A total of 266 NSCLC samples underwent Next Generation Sequencing (NGS) from October 2022 to December 2024. Patients carrying mutation in exon 3 of <i>CTNNB1</i> were compared to a control group of <i>CTNNB1</i>-wild type/<i>EGFR</i>-mutated patients. We analyzed the clinicopathological characteristics and the outcomes of the two groups of patients. <h3>Results:</h3> <i>CTNNB1</i> mutations were identified in 5.3% (14/266) of the cohort. Only 28.6% of these patients had an exclusive <i>CTNNB1</i> mutation, while 71.4% exhibited concomitant mutations, mainly in <i>EGFR</i> gene (42.6%). Patients with <i>CTNNB1</i> mutations were diagnosed at a significantly higher median age (<i>p</i>=0.013) and showed lower PDL1 expression (<i>p</i>=0.036) compared to control group. The <i>CTNNB1</i> mutated patients achieved a median overall survival (OS) of 29 months <i>vs</i>. 23 months in the control group. Interestingly, patients with concurrent <i>EGFR</i> and <i>CTNNB1</i> mutations reached a median OS of 35.5 months; however, this trend did not reach statistical significance due to the small sample size. <h3>Conclusion:</h3> <i>CTNNB1</i> mutations in NSCLC are associated with older age at diagnosis, lower PD-L1 expression and potentially favorable survival outcomes, particularly when appearing alongside <i>EGFR</i> mutations.