Background/Objectives:TP53mutations in advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer could worsen prognosis. Therefore, we aimed to investigate the clinical significance ofTP53mutations and p53 expression in these patients. Methods: Patients with advanced/metastatic EGFR-mutated lung adenocarcinoma treated with first-line tyrosine kinase inhibitors were retrospectively enrolled. Sanger sequencing was performed to detectTP53mutations and immunohistochemical staining was used to verify p53 protein expression levels. Kaplan-Meier and Cox proportional hazards analyses were used to estimate survival and hazard ratio (HR) with 95% confidence interval (CI). Results: The study involved 83 patients with adequate tumor samples forTP53/p53 analysis. Patients with tumor p53 immunostaining ≥50% showed significantly better overall survival (OS) (HR: 0.49 [95% CI: 0.30–0.81],p< 0.001), butTP53mutations were not associated with inferior progression-free survival (PFS) or OS (missense vs. wild-type [PFS, HR: 0.68 (95% CI: 0.40–1.15),p= 0.151; OS, HR: 0.88 (95% CI: 0.56–1.42),p= 0.599]). Areas under the receiver operating characteristic curves ofTP53mutations with different cut-off values for p53 positivity were 0.51–0.56. The Kaplan-Meier survival analysis revealed significant survival benefits in patients with EGFR L858R substitution and tumor p53 immunostaining ≥50% (median PFS: 8.0 vs. 5.3; median OS: 20.4 vs. 15.3 months; log-rankp= 0.025 and 0.049, respectively). Conclusions: Tumor p53 immunostaining (≥50%) was associated with better OS, especially in patients withTP53mutations or L858R. Prospective clinical trials are required to explore the prognostic significance of p53 expression in the genomic era ofTP53mutations.
背景/目的：在晚期表皮生长因子受体（EGFR）突变的非小细胞肺癌中，TP53突变可能恶化预后。因此，本研究旨在探讨TP53突变及p53表达在此类患者中的临床意义。方法：回顾性纳入接受一线酪氨酸激酶抑制剂治疗的晚期/转移性EGFR突变肺腺癌患者。采用Sanger测序检测TP53突变，并通过免疫组化染色验证p53蛋白表达水平。使用Kaplan-Meier法和Cox比例风险模型评估生存期及风险比（HR）与95%置信区间（CI）。结果：本研究共纳入83例具有足量肿瘤样本用于TP53/p53分析的患者。肿瘤p53免疫组化染色≥50%的患者总生存期（OS）显著更优（HR: 0.49 [95% CI: 0.30–0.81], p<0.001），但TP53突变与较差的无进展生存期（PFS）或OS无关（错义突变 vs. 野生型[PFS, HR: 0.68 (95% CI: 0.40–1.15), p=0.151; OS, HR: 0.88 (95% CI: 0.56–1.42), p=0.599]）。不同p53阳性截断值下TP53突变的受试者工作特征曲线下面积为0.51–0.56。Kaplan-Meier生存分析显示，EGFR L858R置换且肿瘤p53免疫组化≥50%的患者生存获益显著（中位PFS：8.0 vs. 5.3个月；中位OS：20.4 vs. 15.3个月；时序检验p值分别为0.025和0.049）。结论：肿瘤p53免疫组化（≥50%）与更好的OS相关，尤其在TP53突变或L858R患者中。未来需开展前瞻性临床试验，以探索TP53突变基因组时代p53表达的预后意义。
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