EGFR mutation status affects intra-tumoural heterogeneity of PD-L1 expression but not agreement between assays in resectable non-small cell lung cancer

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2025-02-27 DOI:10.1016/j.lungcan.2025.108463

Stephanie P.L. Saw , Angela Takano , Siqin Zhou , Nwe Oo Hlaing , Anne James , Craig Joseph , Gillianne G.Y. Lai , Darren W.T. Lim , Ravindran Kanesvaran , Mei-Kim Ang , Quan Sing Ng , Amit Jain , Wan Ling Tan , Yi Lin Teh , Aaron C. Tan , Boon-Hean Ong , Tony K.H. Lim , Joe P.S. Yeong , Sze Huey Tan , Daniel S.W. Tan

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Abstract

Background

The predictive value of PD-L1 to select patients for immunotherapy in resectable NSCLC remains imprecise, confounded by different assays used across trials and intra-tumoural heterogeneity (ITH). We sought to compare the concordance between 3 PD-L1 antibodies stratified by EGFR mutation status, evaluate ITH and implications on survival outcomes.

Methods

Tissue microarrays were constructed from stage IA-IIIA NSCLC with 3 tumour cores per patient. Tumour proportion score (TPS) was evaluated by 3 pathologists for SP263, SP142, 22C3 and analysed in tertiles of < 1 %, 1–49 % and ≥ 50 %. ITH was defined as discordant TPS in ≥ 2/3 tumour cores. Cohen’s kappa test was used to assess agreement. Survival outcomes were estimated using Kaplan-Meier.

Results

A total of 561 patients were included, 59.5% (334/561) were EGFR-mutant. Stage IA comprised 45.5%(255/561), IB 24.1%(135/561), IIA 12.7%(71/561), IIB 4.5%(25/561) and IIIA 13.4%(75/561).

Across 1683 tumour cores, SP263 and 22C3 had the highest concordance (Kappa = 0.689), followed by 22C3 and SP142 (Kappa = 0.354), then SP263 and SP142 (Kappa = 0.284), similar between EGFR-mutant and EGFR-wildtype. Agreement between pathologists was almost perfect.

ITH by SP263 was observed in 14.1 % of EGFR-mutant versus 24.2 % in EGFR-wildtype(p = 0.002). Discordance was highest among TPS 1–49 % at 92.6 % (88/95) followed by ≥ 50 % at 37.8 % (14/37) and least among < 1 % at 0 % (0/429) (p < 0.001). For tumour cores scored 1–49 %, 63 %/70 % of adjacent cores were scored < 1 % for EGFR-wildtype/mutant respectively. Histological grade was the only independent predictor of PD-L1 ITH on multivariable analysis. PD-L1 ITH was not associated with survival on multivariable analysis.

Conclusion

PD-L1 scoring by SP263 and 22C3 are interchangeable but not SP142 regardless of EGFR status. PD-L1 ITH was more common in EGFR-wildtype versus EGFR-mutant tumours. Extra care should be taken to select the most representative tumour core for tumours with high histological grade or TPS 1–49% as this may influence peri-operative treatment decisions.

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背景在可切除的 NSCLC 中，PD-L1 对选择免疫疗法患者的预测价值仍不精确，不同试验中使用的不同检测方法以及肿瘤内异质性（ITH）都会对其产生影响。我们试图比较按表皮生长因子受体突变状态分层的 3 种 PD-L1 抗体之间的一致性，评估 ITH 和对生存结果的影响。肿瘤比例评分（TPS）由 3 位病理学家对 SP263、SP142 和 22C3 进行评估，并按< 1 %、1-49 % 和 ≥ 50 % 三档进行分析。ITH 的定义是≥ 2/3 肿瘤核的 TPS 不一致。科恩卡帕检验用于评估一致性。结果共纳入561例患者，其中59.5%（334/561）为表皮生长因子受体突变。在 1683 个肿瘤核芯中，SP263 和 22C3 的一致性最高（Kappa = 0.在 1683 个肿瘤核芯中，SP263 和 22C3 的一致性最高（Kappa = 0.689），其次是 22C3 和 SP142（Kappa = 0.354），然后是 SP263 和 SP142（Kappa = 0.284），表皮生长因子受体突变型和表皮生长因子受体野生型之间的一致性相似。通过 SP263 观察到的 ITH 在 14.1%的表皮生长因子受体突变型患者和 24.2%的表皮生长因子受体野生型患者中几乎完全一致（P = 0.002）。不一致性在 TPS 1-49 % 中最高，为 92.6 %（88/95），其次是≥ 50 %，为 37.8 %（14/37），而在 < 1 % 中最低，为 0 %（0/429）（p < 0.001）。对于评分为1-49%的肿瘤核芯，63%/70%的相邻核芯的表皮生长因子受体野生型/突变型评分分别为< 1%。在多变量分析中，组织学分级是 PD-L1 ITH 的唯一独立预测因子。结论无论表皮生长因子受体状态如何，SP263和22C3的PD-L1评分均可互换，但SP142不可。PD-L1 ITH在表皮生长因子受体野生型肿瘤和表皮生长因子受体突变型肿瘤中更为常见。对于组织学分级高或TPS 1-49%的肿瘤，应格外注意选择最具代表性的肿瘤核心，因为这可能会影响围手术期的治疗决策。

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

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.