Prognostic Effect of TP53 and PKD Co-Mutations in Patients with Resected Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma.

Abstract

The impact of specific co-mutations in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma is unclear. Tissues from 147 consecutive patients with resected EGFR-mutated lung adenocarcinomas treated at Sun Yat-Sen University Cancer Center were analyzed by next-generation sequencing (NGS). Associations between mutation status, patient baseline characteristics, and survival outcomes (disease-free survival [DFS] and overall survival [OS]) after surgical resection were analyzed. TP53 and protein kinase D (PKD) mutations were the two most frequently observed co-mutations in this cohort. Dual PKD/EGFR and TP53/EGFR mutations were found in 39 (27%) and 72 patients (49%), respectively, with dual TP53/EGFR mutations more commonly observed in male patients (P = 0.021). Both TP53 (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.23-3.54, P = 0.007) and PKD co-mutations (HR 1.72, 95% CI 1.01-2.93, P = 0.044) were associated with shorter DFS, but not OS, in univariate analysis. In multivariate analysis, patients harboring PKD/TP53 co-mutations had shorter DFS compared with PKD-/TP53- cases (HR 2.49, 95% CI 1.15-5.37, P = 0.02). In a subgroup of never-smokers, TP53 co-mutations were associated with significantly worse OS (HR 50.11, 95% CI 2.39-1049.83, P = 0.012). TP53 and PKD mutations were the two most frequently observed co-mutations in resected EGFR-mutated lung adenocarcinoma. Both mutations were associated with poorer prognoses in affected patients.