Agilent Technologies Inc., R&D.
Agilent Technologies Inc., Histopathology, Carpinteria, CA.
Appl Immunohistochem Mol Morphol. 2021 Oct 1;29(9):667-673. doi: 10.1097/PAI.0000000000000941.
Tumor heterogeneity may impact immunohistochemical (IHC) interpretation, thus potentially affecting decision making by treating oncologists for cancer patient management. Programmed cell death ligand-1 (PD-L1) IHC 22C3 pharmDx is a companion diagnostic used as an aid in identifying patient eligibility for treatment with pembrolizumab (KEYTRUDA). This study aims to investigate tumor heterogeneity impact on IHC staining when evaluating PD-L1 expression using PD-L1 IHC 22C3 pharmDx. The effect of tumor heterogeneity was evaluated based on the PD-L1 diagnostic status of PD-L1 IHC 22C3 pharmDx stained tumor tissue sections at relevant diagnostic cutoffs for non-small cell lung carcinoma, gastric or gastroesophageal junction adenocarcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, esophageal cancer and triple negative breast cancer. Overall agreement for the PD-L1 diagnostic status was assessed for each tumor type within a given specimen block (Intra-Block), between specimen blocks from the same surgical resection (Intra-Case), and between intrapatient primary and metastatic specimens. Intrablock and intracase point estimates were above 75%, and primary versus metastatic point estimates were above 50%. The results suggest that PD-L1 expression is consistent across cut sections through a minimum of 150 µm within a tissue block and between blocks from the same surgical resection and is significantly maintained across primary and metastatic blocks from the same patient despite changes to the tissue microenvironment. These data provide confidence for histopathologists and oncologists that evaluation of PD-L1 expression at clinically relevant cutoffs is reproducible among different assessments (or samplings) of a single tumor specimen.
肿瘤异质性可能会影响免疫组织化学（IHC）的解读，从而可能影响治疗肿瘤学家对癌症患者管理的决策。程序性细胞死亡配体-1（PD-L1）IHC 22C3 pharmDx 是一种伴随诊断，用于辅助识别患者是否有资格接受帕博利珠单抗（可瑞达）治疗。本研究旨在探讨使用 PD-L1 IHC 22C3 pharmDx 评估 PD-L1 表达时肿瘤异质性对 IHC 染色的影响。根据非小细胞肺癌、胃或胃食管交界处腺癌、尿路上皮癌、头颈部鳞状细胞癌、食管癌和三阴性乳腺癌的相关诊断截止值，评估 PD-L1 IHC 22C3 pharmDx 染色肿瘤组织切片的 PD-L1 诊断状态的肿瘤异质性的影响。在给定的标本块内（Intra-Block）、来自同一手术切除的标本块之间（Intra-Case）以及同一患者的原发和转移性标本之间，评估每个肿瘤类型的 PD-L1 诊断状态的总体一致性。Intra-Block 和 Intra-Case 的点估计值均高于 75%，而原发与转移的点估计值均高于 50%。结果表明，PD-L1 表达在组织块内的至少 150μm 范围内的不同切片以及来自同一手术切除的标本块之间是一致的，并且在同一患者的原发和转移性标本之间是显著一致的，尽管组织微环境发生了变化。这些数据为病理学家和肿瘤学家提供了信心，即临床相关截止值的 PD-L1 表达评估在单个肿瘤标本的不同评估（或采样）中是可重复的。
