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Updated: May 16, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early-Stage EGFR-Mutated Non-Small Cell Lung
Meejeong Kim1, Gyeong Sin Park1, Kyo Young Lee1
1Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Background:
Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related mortality, with recurrence risks posing significant challenges in early-stage disease management. While epidermal growth factor receptor (EGFR) mutations are common, the role of concurrent genetic alterations remains underexplored, and findings have often been inconsistent, particularly in early-stage tumors.
Methods:
We retrospectively analyzed 424 EGFR-mutated NSCLC patients diagnosed from 2017 to 2022. Next-generation sequencing (NGS) was used to identify genetic alterations, and immunohistochemistry (IHC) was employed to correlate TP53 mutations and EGFR amplification with protein expression. Survival outcomes were assessed using Kaplan-Meier and Cox regression analyses, while predictive cutoffs were determined with receiver operating characteristic (ROC) curve analysis.
Results:
TP53 mutations and EGFR amplification were more prevalent in Stages 2-4 compared to Stage 1 (p < 0.001 and 0.005, respectively). In Stage 1, TP53 mutations, particularly exon 4 and frameshift/nonsense types, were associated with worse overall survival (OS) and disease-free survival (DFS). EGFR amplification was linked to shorter DFS in Stage 1 (p = 0.006). Both alterations correlated with aggressive pathological features, including advanced N stage, lymphovascular invasion, and high histological grade. IHC cutoffs of 15% for TP53 and H-score ≥ 180 for EGFR amplification demonstrated high predictive accuracy (AUC = 0.981 and 0.936, respectively).
Conclusion:
Specific subtypes of TP53 mutations and EGFR amplification are important prognostic markers in early-stage NSCLC. IHC offers a practical surrogate for genetic testing, aiding in risk stratification and guiding adjuvant therapy decisions for high-risk patients. Larger validation studies are warranted.
