程序性死亡配体-1(PD-L1)表达预测非致癌成瘾性肺腺癌(ADC)的免疫治疗效用。然而,在临床试验之外,其可重复性和可靠性可能会受到影响。本研究旨在评估与肺ADC中PD-L1表达相关的因素。
这项观察性研究评估了2016年1月至2020年12月在单个癌症机构中547例晚期肺ADC肿瘤样本。肿瘤样品被至少一个批准的PD-L1克隆染色,SP263(Ventana)或22C3(Dako),并分层肿瘤比例评分(TPS)<1%,1-49%,或≥50%。
在所有的肿瘤样本中,低分化肿瘤中PD-L1阳性染色较高(67.3%vs.32.7%,p<0.001)。与PD-L1高表达(TPS≥50%)相关的分析因素是SP263克隆(19.6%vs.8.2%,p<0.001),存档肿瘤组织时间<12个月(15.3%vs.3.8%,p=0.024),每当最近几年(2019-2020年)进行分析时(19.0%与8.3%,p<0.001),每当由病理学家在学术环境中进行分析时(国立癌症研究所,INCan)(19.9%与11.9%,p=0.001)。在分子分析中,EGFR野生型肿瘤的PD-L1阳性和PD-L1高病例比例增加(60.2%vs.47.9%,p=0.006和17.4%vs.8.5%,p=0.004)。在两种不同的设置(INCan与外部实验室)。
临床病理因素与PD-L1阳性率增加相关。这些差异在PD-L1高组中是显著的,并且与学术环境有关,SPS263克隆,存档肿瘤组织时间<12个月,以及最近的PD-L1分析。
Programmed death ligand-1 (PD-L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD-L1 expression in lung ADC.
This observational study assessed 547 tumor samples with advanced lung ADC from January 2016 to December 2020 in a single cancer institution. Tumor samples were stained by at least one approved PD-L1 clone, SP263 (Ventana) or 22C3 (Dako), and stratified in tumor proportion score (TPS) <1%, 1-49%, or ≥50%.
Of all the tumor samples, positive PD-L1 staining was higher in poorly differentiated tumors (67.3% vs. 32.7%, p < 0.001). Analytical factors associated with a PD-L1 high expression (TPS ≥ 50%) were the SP263 clone (19.6% vs. 8.2%, p < 0.001), time of archival tumor tissue <12 months (15.3% vs. 3.8%, p = 0.024), whenever the analysis was performed in the most recent years (2019-2020) (19.0% vs. 8.3%, p < 0.001), and whenever the analysis was performed by pathologists in the academic setting (Instituto Nacional de Cancerologia, INCan) (19.9% vs. 11.9%, p = 0.001). In the molecular analysis, EGFR wild-type tumors had an increased proportion of PD-L1 positive and PD-L1 high cases (60.2% vs. 47.9%, p = 0.006 and 17.4% vs.8.5%, p = 0.004). A moderate correlation (r = 0.69) in the PD-L1 TPS% was observed between the two different settings (INCan vs. external laboratories).
Clinicopathological factors were associated with an increased PD-L1 positivity rate. These differences were significant in the PD-L1 high group and associated with the academic setting, the SPS263 clone, time of archival tumor tissue <12 months, and a more recent period in the PD-L1 analysis.