Automated Tumour Recognition and Digital Pathology Scoring Unravels New Role for PD-L1 in Predicting Good Outcome in ER-/HER2+Breast Cancer
Automated Tumour Recognition and Digital Pathology Scoring Unravels New Role for PD-L1 in Predicting Good Outcome in ER-/HER2+Breast Cancer
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DOI：
10.1155/2018/2937012
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Buckley, Niamh E.
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文献类型：
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作者：
Humphries, Matthew P.;Hynes, Sean;Buckley, Niamh E.
PD-L1作为预后和预测生物标志物的作用是一个非常感兴趣的领域。然而，关于如何将PD-L1作为临床生物标志物递送缺乏共识。这个难题的核心是迄今为止大多数研究中PD-L1 IHC的主观评分。目前的标准评分系统涉及上皮细胞和炎性细胞的分离，并在不同的表达百分比中发现临床意义，例如，高于或低于1%。显然，一种客观、可重复和准确的PD-L1评分方法将为这种情况带来一定程度的必要一致性。通过对技术的系统比较和数字病理学平台QuPath的应用，我们发现PD-L1的高表达与标准治疗（SoC）化疗背景下三阴性乳腺癌的临床结局改善相关，这与之前的研究结果一致。此外，我们首次证明PD-L1高表达也与ER-疾病（包括HER 2+乳腺癌）的整体结局更好相关。我们证明了抗体选择对定量和临床影响的影响，Ventana抗体（SP142）提供了我们手中最稳健的检测方法。通过对肿瘤的不同区域进行采样，我们发现肿瘤富集区域显示出最大范围的PD-L1表达，与基质和淋巴富集区域相比，这具有最大的临床意义。此外，我们观察到炎症和上皮PD-L1表达与化疗背景下生存率的改善相关。此外，正如PD-L1抑制剂研究所见，PD-L1表达的低阈值对患者结果产生分层。这强调了使用数字病理学和精确的生物标志物定量来实现可以区分低PD-L1表达的准确和可重复评分的重要性。
The role of PD-L1 as a prognostic and predictive biomarker is an area of great interest. However, there is a lack of consensus on how to deliver PD-L1 as a clinical biomarker. At the heart of this conundrum is the subjective scoring of PD-L1 IHC in most studies to date. Current standard scoring systems involve separation of epithelial and inflammatory cells and find clinical significance in different percentages of expression, e.g., above or below 1%. Clearly, an objective, reproducible and accurate approach to PD-L1 scoring would bring a degree of necessary consistency to this landscape. Using a systematic comparison of technologies and the application of QuPath, a digital pathology platform, we show that high PD-L1 expression is associated with improved clinical outcome in Triple Negative breast cancer in the context of standard of care (SoC) chemotherapy, consistent with previous findings. In addition, we demonstrate for the first time that high PD-L1 expression is also associated with better outcome in ER- disease as a whole including HER2+ breast cancer. We demonstrate the influence of antibody choice on quantification and clinical impact with the Ventana antibody (SP142) providing the most robust assay in our hands. Through sampling different regions of the tumour, we show that tumour rich regions display the greatest range of PD-L1 expression and this has the most clinical significance compared to stroma and lymphoid rich areas. Furthermore, we observe that both inflammatory and epithelial PD-L1 expression are associated with improved survival in the context of chemotherapy. Moreover, as seen with PD-L1 inhibitor studies, a low threshold of PD-L1 expression stratifies patient outcome. This emphasises the importance of using digital pathology and precise biomarker quantitation to achieve accurate and reproducible scores that can discriminate low PD-L1 expression.