Department of Pathology, University of Chicago, Chicago, IL 60637.
Department of Pathology, University of Utah, Salt Lake City, UT 84112; ARUP Laboratories, Salt Lake City, UT, 84108.
Hum Pathol. 2019 May;87:11-17. doi: 10.1016/j.humpath.2019.02.001. Epub 2019 Feb 20.
Malignant mesothelioma (MM) is an aggressive neoplasm with poor prognosis. The Dako PD-L1 22C3 and 28-8 pharmDx assays are approved by the US Food and Drug Administration (FDA) as companion and complementary diagnostics for the anti-PD-1 drugs pembrolizumab and nivolumab, respectively. Data from multiple clinical trials indicate that immunotherapy has antitumor activity in advanced malignant pleural (MPM) and peritoneal mesothelioma (MPeM). However, large studies of PD-L1 expression in MM using the FDA-approved anti-PD-L1 assays are lacking. We stained tissue microarray sections (N = 125; 112 MPM and 13 MPeM) using 2 FDA-approved clinical immunohistochemical makers for PD-L1 expression: Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx. Overall, 22% (27/125) of MMs were positive using the 22C3 assay, whereas 27% (32/117) were positive using the 28-8 assay, using a tumor proportion score cutoff of 1%. Tumor cell PD-L1 expression was strongly correlated with PD-L1 expression on tumor-associated immune cells. No significant difference in PD-L1 expression was observed by patient sex, age, treatment history, pathologic stage, or histologic subtype. However, the proportion of cases positive for PD-L1 expression was higher among MPeM compared to MPM (P = .007 for 22C3 assay; P = .04 for 28-8 assay). PD-L1 is expressed in a substantial proportion of MM cases, as measured by FDA-approved companion assays for widely used immunotherapeutic drugs. PD-L1 expression is particularly prevalent in MPeM. These findings support large clinical studies to further examine PD-L1 as a biomarker for a subset of MM patients that may benefit from immunotherapy.
恶性间皮瘤（MM）是一种侵袭性肿瘤，预后不良。Dako PD-L1 22C3 和 28-8 pharmDx 检测试剂盒已获得美国食品和药物管理局（FDA）批准，分别作为抗 PD-1 药物 pembrolizumab 和 nivolumab 的伴随诊断和补充诊断。多项临床试验数据表明，免疫疗法对晚期恶性胸膜（MPM）和腹膜间皮瘤（MPeM）具有抗肿瘤活性。然而，缺乏使用 FDA 批准的抗 PD-L1 检测试剂盒对 MM 中 PD-L1 表达进行的大型研究。我们使用 2 种 FDA 批准的用于 PD-L1 表达的临床免疫组织化学标记物对组织微阵列切片（N=125；112 例 MPM 和 13 例 MPeM）进行染色：Dako PD-L1 22C3 pharmDx 和 Dako PD-L1 28-8 pharmDx。总体而言，使用 22C3 检测试剂盒，22%（27/125）的 MM 为阳性，而使用 28-8 检测试剂盒，27%（32/117）的 MM 为阳性，肿瘤比例评分截断值为 1%。肿瘤细胞 PD-L1 表达与肿瘤相关免疫细胞上的 PD-L1 表达呈强相关性。患者性别、年龄、治疗史、病理分期或组织学亚型对 PD-L1 表达无显著影响。然而，与 MPM 相比，MPeM 中 PD-L1 表达阳性的病例比例更高（22C3 检测试剂盒 P=0.007；28-8 检测试剂盒 P=0.04）。在使用广泛的免疫治疗药物的 FDA 批准的伴随检测试剂盒中，相当一部分 MM 病例中表达 PD-L1。PD-L1 在 MPeM 中更为普遍。这些发现支持进一步研究 PD-L1 作为一组 MM 患者生物标志物的大型临床研究，这些患者可能受益于免疫治疗。
