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

作者：Stephanie P.L. Saw, Angela Takano, Siqin Zhou, Nwe Oo Hlaing, Anne James, Craig Joseph, Gillianne Lai, Wan‐Teck Lim, Ravindran Kanesvaran, Mei‐Kim Ang, Quan Sing Ng, Amit Jain, Wan Ling Tan, Yi Lin Teh, Aaron C. Tan, Boon‐Hean Ong, Tony Kiat Hon Lim, Joe Yeong, Sze Huey Tan, Daniel S.W. Tan · 发表于：Lung Cancer · 年份：2025 · DOI：10.1016/j.lungcan.2025.108463 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Treatments and Mutations、Radiomics and Machine Learning in Medical Imaging

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 %/...