Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker
ABSTRACT 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 alterati...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.70058 |
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| author | Meejeong Kim Gyeong Sin Park Kyo Young Lee Seok Whan Moon Yeoun Eun Sung |
| author_facet | Meejeong Kim Gyeong Sin Park Kyo Young Lee Seok Whan Moon Yeoun Eun Sung |
| author_sort | Meejeong Kim |
| collection | DOAJ |
| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-334bed2e51b245eaa65d228c5ad227e4 |
| institution | OA Journals |
| issn | 1759-7706 1759-7714 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj-art-334bed2e51b245eaa65d228c5ad227e42025-08-20T02:12:25ZengWileyThoracic Cancer1759-77061759-77142025-04-01167n/an/a10.1111/1759-7714.70058Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate MarkerMeejeong Kim0Gyeong Sin Park1Kyo Young Lee2Seok Whan Moon3Yeoun Eun Sung4Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of KoreaDepartment of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of KoreaDepartment of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of KoreaDepartment of Thoracic and Cardiovascular Surgery, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of KoreaDepartment of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of KoreaABSTRACT 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.https://doi.org/10.1111/1759-7714.70058early‐stage lung cancerEGFR amplificationEGFR mutationnon‐small cell lung cancer (NSCLC)TP53 mutation |
| spellingShingle | Meejeong Kim Gyeong Sin Park Kyo Young Lee Seok Whan Moon Yeoun Eun Sung Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker Thoracic Cancer early‐stage lung cancer EGFR amplification EGFR mutation non‐small cell lung cancer (NSCLC) TP53 mutation |
| title | Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker |
| title_full | Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker |
| title_fullStr | Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker |
| title_full_unstemmed | Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker |
| title_short | Role of TP53 Mutations and EGFR Amplification in Risk Stratification of Early‐Stage EGFR‐Mutated Non‐Small Cell Lung Cancer With Immunohistochemistry as a Surrogate Marker |
| title_sort | role of tp53 mutations and egfr amplification in risk stratification of early stage egfr mutated non small cell lung cancer with immunohistochemistry as a surrogate marker |
| topic | early‐stage lung cancer EGFR amplification EGFR mutation non‐small cell lung cancer (NSCLC) TP53 mutation |
| url | https://doi.org/10.1111/1759-7714.70058 |
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