FDA批准的程序性死亡受体配体1(PD-L1)检测方法在肾透明细胞癌中的诊断一致性评估

Evaluation of the diagnostic concordance of FDA-approved PD-L1 assays in clear cell renal cell carcinoma.

作者信息

Koh Yoko, Kato Taigo, Yamamichi Gaku, Tomiyama Eisuke, Matsushita Makoto, Hatano Koji, Kawashima Atsunari, Nonomura Norio, Uemura Motohide

机构信息

Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Department of Urology, Fukushima Medical University School of Medicine, 1, Hikarigaoka, Fukushima, 960-1295, Japan.

出版信息

Sci Rep. 2025 Jul 1;15(1):21253. doi: 10.1038/s41598-025-05697-4.

Abstract

Therapeutic strategies for advanced renal cell carcinoma have advanced dramatically since the approval of immune checkpoint inhibitors. To date, four PD-L1 assays have been established as companion diagnostic tools for checkpoint inhibitors. However, all PD-L1 assays present several limitations in terms of concordance and compatibility. In this study, we constructed tissue microarrays from 286 clear cell renal cell carcinoma (ccRCC) tissue samples and evaluated PD-L1 expression using the 22C3, 28 - 8, SP142, and SP263 PD-L1 assays. Detection of PD-L1 expression in tumor cells was very low for all PD-L1 assays tested, although expression of PD-L1 in immune cells in the tumor area was 14.7% for 22C3, 16.1% for 28 - 8, 2.1% for SP142, and 15.0% for SP263. PD-L1 expression on immune cells assessed by 28 - 8 showed a moderate pairwise concordance with other assays (κ statistics: 0.52 with 22C3, 0.16 with SP142, and 0.46 with SP263). Patients with PD-L1 expression in immune cells evaluated using 22C3, 28 - 8, and SP263 showed significantly worse cancer-specific survival. PD-L1 expression on renal cell carcinoma tissues assessed using 22C3, 28 - 8, SP142, and SP263 did not show good concordance. In conclusion, differences between these assays should be considered when evaluating the results of immunohistochemical findings.

摘要

自免疫检查点抑制剂获批以来,晚期肾细胞癌的治疗策略取得了显著进展。迄今为止,已有四种PD-L1检测方法被确立为检查点抑制剂的伴随诊断工具。然而,所有PD-L1检测方法在一致性和兼容性方面都存在一些局限性。在本研究中,我们用286份透明细胞肾细胞癌(ccRCC)组织样本构建了组织微阵列,并使用22C3、28-8、SP142和SP263这几种PD-L1检测方法评估了PD-L1的表达情况。在所检测的所有PD-L1检测方法中,肿瘤细胞中PD-L1表达的检测率都非常低,不过肿瘤区域免疫细胞中PD-L1的表达率在22C3检测中为14.7%,在28-8检测中为16.1%,在SP142检测中为2.1%,在SP263检测中为15.0%。通过28-8检测评估的免疫细胞上的PD-L1表达与其他检测方法显示出中等程度的成对一致性(κ统计值:与22C3为0.52,与SP142为0.16,与SP263为0.46)。使用22C3、28-8和SP263评估的免疫细胞中PD-L1表达的患者显示出明显更差的癌症特异性生存率。使用22C3、28-8、SP142和SP263评估的肾细胞癌组织上的PD-L1表达并未显示出良好的一致性。总之,在评估免疫组化结果时应考虑这些检测方法之间的差异。

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