Department of Molecular and Clinical Cancer Medicine, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK; Department of Cellular Pathology, Royal Liverpool University Hospital, Duncan Building, Daulby Street, Liverpool, L7 8XP, UK.
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
Lung Cancer. 2019 Aug;134:79-84. doi: 10.1016/j.lungcan.2019.06.005. Epub 2019 Jun 5.
PD-L1 expression on tumour cells can guide the use of anti-PD-1/PD-L1 immune modulators to treat patients with non-small cell lung cancer (NSCLC). Heterogeneity of PD-L1 expression both within and between tumour sites is a well-documented phenomenon that compromises its predictive power. Our aim was to better characterise the pattern and extent of PD-L1 heterogeneity with a view to optimising tumour sampling and improve its accuracy as a biomarker.
Expression of PD-L1 was assessed by immunochemistry using the SP263 clone in 107 resected primary NSCLCs and their nodal metastases. Intra-tumoural heterogeneity, defined as 'small-scale' (mm²), 'medium-scale' (cm²) and 'large-scale' (between tumour blocks), was assessed by digital imaging using a novel 'squares method'. Inter-tumoural heterogeneity between the primary tumours and their nodal metastases and between N1 and N2 nodal stages was also assessed.
The majority of tumours demonstrated intra-tumoural heterogeneity (small-scale 78%, medium-scale 50%, large-scale 46%). Inter-tumoural heterogeneity between the primary and nodal metastases was present in 53% of cases and, in 17%, between N1 and N2 disease. These differences were occasionally sufficient to lead to discrepancy across the ≥1%, ≥25% and ≥50% cut-offs used to guide therapy.
Heterogeneity of PD-L1 expression is common, variable in scale and extent, and carries significant implications for its accuracy as a predictive biomarker. Extensive sampling reduces, but cannot eliminate, this inaccuracy.
肿瘤细胞上 PD-L1 的表达可指导使用抗 PD-1/PD-L1 免疫调节剂来治疗非小细胞肺癌（NSCLC）患者。肿瘤内和肿瘤间 PD-L1 表达的异质性是一个有据可查的现象，这降低了其预测能力。我们的目的是更好地描述 PD-L1 异质性的模式和程度，以期优化肿瘤取样，并提高其作为生物标志物的准确性。
使用 SP263 克隆通过免疫组织化学评估 107 例切除的原发性 NSCLC 及其淋巴结转移中的 PD-L1 表达。通过使用新型“方格法”的数字成像评估肿瘤内异质性，定义为“小尺度”（mm²）、“中尺度”（cm²）和“大尺度”（肿瘤块之间）。还评估了原发性肿瘤与其淋巴结转移之间以及 N1 和 N2 淋巴结分期之间的肿瘤间异质性。
大多数肿瘤显示出肿瘤内异质性（小尺度 78%、中尺度 50%、大尺度 46%）。原发性和淋巴结转移之间存在肿瘤间异质性，在 53%的病例中，在 17%的病例中，N1 和 N2 疾病之间存在异质性。这些差异偶尔足以导致指导治疗的≥1%、≥25%和≥50%的临界值之间出现差异。
PD-L1 表达的异质性很常见，程度和规模各不相同，这对其作为预测生物标志物的准确性有重大影响。广泛取样可减少但不能消除这种不准确性。
