Prognostic implications of MDM2 expression in surgically resected epidermal growth factor receptor mutant lung cancer with pathological lymph node metastasis.

IF 3.5 2区医学 Q2 ONCOLOGY

Translational lung cancer research Pub Date : 2025-07-31 Epub Date: 2025-07-28 DOI:10.21037/tlcr-2025-143

Tetsuya Isaka, Yohei Miyagi, Rika Kasajima, Kota Washimi, Shuji Murakami, Haruhiro Saito, Yui Sueishi, Naoko Shigeta, Ikki Takada, Ryotaro Matsuyama, Chiaki Kanno, Takuya Nagashima, Hiroyuki Ito

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引用次数: 0

Abstract

Background: MDM2 protein regulates p53 protein activity; however, the prognostic impact of MDM2 expression in primary lung cancer on patient prognoses is unknown. This study investigated the prognostic implications of MDM2 protein expression among patients with epidermal growth factor receptor mutant (EGFRm) lung adenocarcinoma with pathologic lymph node metastases after surgery.

Methods: Immunohistochemical analysis was conducted to determine the MDM2 expression of pN1-N2 EGFRm [exon 19 deletion mutation (Ex19) and exon 21 L858R mutation (Ex21)] lung cancer that were surgically resected between January 2010 and December 2020 (n=124). The postoperative prognosis and cumulative incidence of recurrence were retrospectively analyzed.

Results: MDM2 protein expression was positive in 56 patients (45.2%) with EGFRm lung adenocarcinoma. The relapse-free survival (RFS) rate was significantly better among patients with MDM2⁺ vs. those with MDM2^- (5-year RFS: 35.5% vs. 14.8%, P=0.04). Multivariable analysis revealed MDM2⁺ as an independent favorable prognostic factor for RFS [hazard ratio (HR), 0.64; 95% confidence interval (CI): 0.42-0.98; P=0.04]. Among patients with Ex21 lung cancer (n=63), significantly better RFS and overall survival (OS) were seen in patients with MDM2⁺ than those with MDM2^- (5-year RFS: 36.4% vs. 9.2%, P=0.005; 5-year OS: 81.8% vs. 39.3%, P=0.002). Multivariable analysis revealed that among patients with Ex21 lung cancer, MDM2⁺ was an independent favorable prognostic factor for RFS (HR, 0.43; 95% CI: 0.23-0.80; P=0.008) and OS (HR, 0.32; 95% CI: 0.15-0.67; P=0.003), and it was also associated with a low cumulative incidence of overall distant recurrence (HR, 0.42; 95% CI: 0.20-0.87; P=0.02) and central nervous system recurrence (HR, 0.23; 95% CI: 0.07-0.80; P=0.02).

Conclusions: MDM2 protein expression is a prognostic predictor of RFS and OS in patients with pN1-N2 Ex21 lung cancer after curative surgery. MDM2 can be a novel biomarker for predicting postoperative prognosis and distant metastasis, especially in the central nervous system.

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MDM2表达在手术切除的伴有病理性淋巴结转移的表皮生长因子受体突变型肺癌中的预后意义。

背景：MDM2蛋白调控p53蛋白活性；然而，MDM2在原发性肺癌中表达对患者预后的影响尚不清楚。本研究探讨了表皮生长因子受体突变（EGFRm）肺腺癌术后伴病理性淋巴结转移患者MDM2蛋白表达的预后意义。方法：采用免疫组化方法检测2010年1月至2020年12月手术切除的肺癌患者pN1-N2 EGFRm[外显子19缺失突变（Ex19）和外显子21 L858R突变（Ex21）] （n=124）的MDM2表达。回顾性分析两组患者术后预后及累计复发率。结果：56例EGFRm肺腺癌患者（45.2%）MDM2蛋白表达阳性。MDM2+组患者的无复发生存率（RFS）明显优于MDM2-组（5年RFS: 35.5% vs 14.8%， P=0.04）。多变量分析显示MDM2+是RFS的独立有利预后因素[危险比（HR）， 0.64；95%置信区间（CI）： 0.42-0.98；P = 0.04)。在Ex21肺癌患者（n=63）中，MDM2+组患者的RFS和总生存期（OS）明显优于MDM2-组(5年RFS: 36.4% vs. 9.2%， P=0.005；5年OS: 81.8% vs. 39.3%， P=0.002)。多变量分析显示，在Ex21肺癌患者中，MDM2+是RFS的独立有利预后因素(HR, 0.43；95% ci: 0.23-0.80；P=0.008)和OS (HR, 0.32；95% ci: 0.15-0.67；P=0.003)，也与较低的总远处复发率相关(HR, 0.42；95% ci: 0.20-0.87；P=0.02)和中枢神经系统复发(HR, 0.23；95% ci: 0.07-0.80；P = 0.02)。结论：MDM2蛋白表达是pN1-N2 Ex21肺癌根治性手术后患者RFS和OS的预后预测因子。MDM2可以作为预测术后预后和远处转移的一种新的生物标志物，特别是在中枢神经系统。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational lung cancer research Medicine-Oncology

CiteScore

7.20

自引率

2.50%

发文量

137

期刊介绍： Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.