Parra Edwin R, Villalobos Pamela, Rodriguez-Canales Jaime
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Appl Immunohistochem Mol Morphol. 2019 Apr;27(4):287-294. doi: 10.1097/PAI.0000000000000602.
Preliminary data suggest that tumor expression of programmed cell death ligand 1 (PD-L1) protein in human cancers, as determined by immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples, may predict clinical response to anti-PD-1/PD-L1 therapy. PD-L1 is not a specific tumor marker and its expression is also observed in various nonmalignant cells, such as macrophages and lymphocytes, causing confusion in immunohistochemistry analysis when these inflammatory cells are overlapping with tumors cells. The aim of the current study was to examine PD-L1 expression in formalin-fixed, paraffin-embedded malignant and nonmalignant cells from human tumors to establish potential characteristic patterns of PD-L1 expression in tumor tissues. We used a commercial PD-L1 clone (E1L3N) previously validated in our laboratory to characterize PD-L1 expression in surgically resected lung adenocarcinomas, lung squamous cell carcinomas, malignant melanomas, renal cell carcinomas, hepatocellular carcinomas, and ductal breast carcinomas. We observed different patterns of PD-L1 expression by malignant cells and nonmalignant cells as membrane, cytoplasmic, and nuclear expression. The distribution of expression was variable including the entire malignant cells population, heterogonous with random distribution, peripheral distribution, minimal expression by few cells and negative expression. Similar, nonmalignant cells showed randomly and peripherally distribution through the tumors. We concluded that the PD-L1 cell protein expression patterns and distributions are variable and differ between resected tumor specimens. The expression and distribution pattern described here provide a useful knowledgment of PD-L1 expression in tumor samples.
初步数据表明，通过对福尔马林固定、石蜡包埋的组织样本进行免疫组织化学检测，人类癌症中程序性细胞死亡配体1（PD-L1）蛋白的肿瘤表达可能预测对抗PD-1/PD-L1治疗的临床反应。PD-L1不是一种特异性肿瘤标志物，在各种非恶性细胞如巨噬细胞和淋巴细胞中也可观察到其表达，当这些炎症细胞与肿瘤细胞重叠时，会在免疫组织化学分析中造成混淆。本研究的目的是检测福尔马林固定、石蜡包埋的人类肿瘤恶性和非恶性细胞中PD-L1的表达，以确定肿瘤组织中PD-L1表达的潜在特征模式。我们使用了先前在我们实验室中验证过的商业PD-L1克隆（E1L3N）来表征手术切除的肺腺癌、肺鳞状细胞癌、恶性黑色素瘤、肾细胞癌、肝细胞癌和乳腺导管癌中PD-L1的表达。我们观察到恶性细胞和非恶性细胞的PD-L1表达模式不同，表现为膜表达、细胞质表达和核表达。表达分布各不相同，包括整个恶性细胞群体、随机分布的异质性、周边分布、少数细胞的低表达和阴性表达。类似地，非恶性细胞在肿瘤中呈随机和周边分布。我们得出结论，PD-L1细胞蛋白表达模式和分布各不相同，在切除的肿瘤标本之间存在差异。这里描述的表达和分布模式为肿瘤样本中PD-L1的表达提供了有用的认识。
