Kim Meejeong, Park Gyeong Sin, Lee Kyo Young, Moon Seok Whan, Sung Yeoun Eun
Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Thoracic and Cardiovascular Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Thorac Cancer. 2025 Apr;16(7):e70058. doi: 10.1111/1759-7714.70058.
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.
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.
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).
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.
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因，复发风险在早期疾病管理中构成重大挑战。虽然表皮生长因子受体（EGFR）突变很常见，但同时发生的基因改变的作用仍未得到充分探索，研究结果往往不一致，尤其是在早期肿瘤中。
我们回顾性分析了2017年至2022年诊断的424例EGFR突变的NSCLC患者。采用二代测序（NGS）鉴定基因改变，采用免疫组织化学（IHC）将TP53突变和EGFR扩增与蛋白表达相关联。使用Kaplan-Meier和Cox回归分析评估生存结果，同时通过受试者操作特征（ROC）曲线分析确定预测临界值。
与1期相比，TP53突变和EGFR扩增在2-4期更为普遍（分别为p < 0.001和0.005）。在1期，TP53突变，特别是外显子4以及移码/无义类型，与较差的总生存期（OS）和无病生存期（DFS）相关。EGFR扩增与1期较短的DFS相关（p = 0.006）。这两种改变均与侵袭性病理特征相关，包括晚期N分期、淋巴血管侵犯和高组织学分级。TP53的IHC临界值为15%，EGFR扩增的H评分≥180显示出较高的预测准确性（AUC分别为0.981和0.936）。
TP53突变和EGFR扩增的特定亚型是早期NSCLC的重要预后标志物。IHC为基因检测提供了一种实用的替代方法，有助于风险分层并指导高危患者的辅助治疗决策。需要进行更大规模的验证研究。
