Department of Pathology, CORE Diagnostics, 406, Udyog Vihar III, Gurgaon, Haryana 122001, India.
Indian Council of Medical Research and National Institute of Malaria Research, New Delhi, 110029, India.
Pathol Res Pract. 2021 Dec;228:153497. doi: 10.1016/j.prp.2021.153497. Epub 2021 May 24.
Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients.
Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations.
PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors.
This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.
针对细胞免疫检查点的程序性死亡受体-1（PD-1）和程序性死亡配体-1（PD-L1）抗体的免疫疗法是目前的研究热点，在晚期非小细胞肺癌（NSCLC）患者中显示出有前景的结果。由于缺乏来自印度视角的 PD-L1 表达数据，我们研究了这些患者的临床病理特征和致癌驱动突变之间的相关性。
使用兔抗人 PD-L1 单克隆抗体（克隆 SP263）对 252 例晚期 NSCLC 患者的样本进行 PD-L1 表达的免疫组织化学检测，在 Ventana BenchMark ULTRA 自动染色仪上进行。同时，通过下一代测序（EGFR、ALK、ROS、MET 和 BRAF）研究遗传突变。分析 PD-L1 表达与临床病理特征和各种突变的关系。
134 例患者（53.2%）PD-L1 阳性。男性比女性更为常见，为两倍。PD-L1 表达与年龄、性别、检测部位（原发性与转移性肿瘤）、吸烟状况、肿瘤侧位、分期或组织学类型之间无显著相关性；然而，实性和腺泡型腺癌与其他腺癌亚型相比具有显著差异（p=0.013），高分化和中分化与低分化肿瘤相比具有显著差异（p=0.022）。当比较 PD-L1 阳性（≥25%）的类型/程度与人口统计学、临床和病理变量时，在肿瘤分级（高分级与低分级）（p=0.009）和分期（p=0.039）方面观察到显著差异。PD-L1 表达与致癌驱动因素无统计学意义。高 PD-L1 表达（TPS≥50%）见于 27.6%的患者，女性（32.4%）、≥60 岁（33.8%）、吸烟者（27.3%）、低分化（36.8%）和 IV 期肿瘤（28.2%）更为常见。外显子 19 缺失在 PD-L1 阴性肿瘤中更为常见，而外显子 21 替换（L858R）在 PD-L1 阳性肿瘤中更为常见。
这是印度最大的研究，比较了 PD-L1 表达与 NSCLC 患者的临床病理和基因组参数。PD-L1 表达与高级别、实性和腺泡型腺癌以及晚期肿瘤显著相关。高 PD-L1 表达在女性患者、≥60 岁、吸烟者和低分化及 IV 期肿瘤（28.2%）中更为常见。外显子 19 缺失在 PD-L1 阴性肿瘤中更为常见，而外显子 21 替换（L858R）在 PD-L1 阳性肿瘤中更为常见。PD-L1 是一种潜在的预测标志物，可对受益于 PD-1 通路靶向治疗的患者进行分层。
