Molecular Pathology Diagnostic Service, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.
Pathol Oncol Res. 2020 Jan;26(1):79-89. doi: 10.1007/s12253-018-0469-6. Epub 2018 Sep 17.
PD-L1 expression testing is mandatory prior to pembrolizumab prescription in non-small cell lung cancer. Our service offers PD-L1 testing using the PD-L1 IHC 22C3 pharmDx assay, in parallel with EGFR, ALK, ROS1 and (in some cases) KRAS testing. We correlate PD-L1 expression in 10,005 tumours with patient age and sex, with tumour histological subtypes, with the sampling modality and type of tissue, and with the presence of other molecular alterations. PD-L1 expression testing was performed using the aforementioned assay; tumour proportion scores (TPS) of 1 and 50% were taken as cut-offs for low and high positivity, respectively. EGFR testing was performed using the cobas® EGFR Mutation Test v2. ALK testing was performed using the VENTANA ALK (D5F3) CDx Assay. KRAS testing was performed using pyrosequencing. TPS <1% was seen in 44.4% of tumours, 1-49% in 25.0% and ≥ 50% in 30.6%. We identified no significant relationship with age. Female patients were slightly more likely to express PD-L1. Poorly-differentiated tumour histology and ALK translocation were significantly associated with PD-L1 expression. Rare EGFR mutations tended to be associated with PD-L1 expression. Pleural and nodal metastases were more likely to express PD-L1 than primary tumours, but biopsy and cytological specimens did not show different PD-L1 expression rates. Our data show that the means of acquiring a tumour sample (biopsy versus cytology) does not have a significant impact on PD-L1 expression. However, we found that certain metastatic sites were associated with significantly higher expression rates, which has substantial implications for selection of tissue for testing.
PD-L1 表达检测是在非小细胞肺癌患者使用帕博利珠单抗治疗之前必须进行的。我们的服务提供 PD-L1 检测，使用 PD-L1 IHC 22C3 pharmDx 检测试剂盒，同时进行 EGFR、ALK、ROS1 检测，以及在某些情况下进行 KRAS 检测。我们将 10005 个肿瘤的 PD-L1 表达与患者的年龄和性别、肿瘤组织学亚型、采样方式和组织类型以及其他分子改变进行了相关性分析。PD-L1 表达检测使用了上述检测试剂盒；肿瘤比例评分（TPS）为 1 和 50%分别被视为低阳性和高阳性的截断值。EGFR 检测使用 cobas® EGFR Mutation Test v2。ALK 检测使用 VENTANA ALK（D5F3）CDx 试剂盒。KRAS 检测使用焦磷酸测序。TPS<1%见于 44.4%的肿瘤，1-49%见于 25.0%，≥50%见于 30.6%。我们没有发现年龄与 PD-L1 表达有显著关系。女性患者更有可能表达 PD-L1。低分化肿瘤组织学和 ALK 易位与 PD-L1 表达显著相关。罕见的 EGFR 突变与 PD-L1 表达呈正相关。胸膜和淋巴结转移比原发性肿瘤更有可能表达 PD-L1，但活检和细胞学标本的 PD-L1 表达率没有差异。我们的数据表明，获取肿瘤样本的方法（活检与细胞学）对 PD-L1 表达没有显著影响。然而，我们发现某些转移部位的表达率显著更高，这对选择用于检测的组织具有重要意义。
