David G. Cogan Ophthalmic Pathology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA; Ophthalmic Plastic and Reconstructive Surgery Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.
David G. Cogan Ophthalmic Pathology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.
Am J Ophthalmol. 2020 Dec;220:128-139. doi: 10.1016/j.ajo.2020.07.031. Epub 2020 Jul 28.
To evaluate the expression of programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) in ocular adnexal sebaceous carcinoma (OASC), and to appraise these findings within the context of recent comparable studies.
Retrospective case series.
Twenty cases of primary OASC were immunostained for PD-L1, PD-L2 and CD8. PD-L1 and PD-L2 expression were graded with both the combined positive score (CPS) and the tumor proportion score (TPS). Both raw CPS and TPS were reported, as well as positivity with TPS and CPS ≥1. CD8 expression was graded on a 0-3 scale. Charts were reviewed for clinical correlations. The results of the current study were compared with results of similar recent investigations.
For the 20 cases, mean expression of PD-L1 with CPS was 29.7 (range 0-101.5) and with TPS was 12.2 (range 0-95.8); mean expression of PD-L2 with CPS was 7.9 (range 0-37.3) and with TPS was 1.9 (range 0-12.9). PD-L1 CPS ≥1 was detected in 95% of OASC, while PD-L1 TPS ≥1 was found in 75%. PD-L2 CPS ≥1 was present in 60%, while only 20% had PD-L2 TPS ≥1. Immune cells appeared to contribute to a substantial proportion of PD-L1 and PD-L2 positivity, and a conspicuous CD8-positive T-lymphocytic infiltrate was present in most tumors. Significant correlations were identified between tissue expression of PD-L1, PD-L2, and CD8. Tissues with greater levels of PD-L1 tended to express higher levels of PD-L2 and CD8. The degree of PD-L1 and PD-L2 expression was also associated with the area in millimeters squared of the immunostained tumor, suggesting that tumor sampling may influence interpretation of PD-L1 and PD-L2 expression in ocular adnexal tumors.
The current and preceding studies confirm that PD-L1 and PD-L2 are expressed in a high percentage of OASCs. These results support the premise that checkpoint inhibitor drugs hold considerable therapeutic promise for patients with OASC and stimulate the institution of clinical trials.
评估程序性死亡配体 1（PD-L1）和程序性死亡配体 2（PD-L2）在眼附属器皮脂腺癌（OASC）中的表达，并在最近的类似研究背景下评估这些发现。
回顾性病例系列。
对 20 例原发性 OASC 进行 PD-L1、PD-L2 和 CD8 的免疫染色。采用联合阳性评分（CPS）和肿瘤比例评分（TPS）对 PD-L1 和 PD-L2 的表达进行分级。报告了原始 CPS 和 TPS，以及 TPS 和 CPS≥1 的阳性率。CD8 表达按 0-3 级评分。回顾图表以获取临床相关性。将当前研究的结果与最近类似研究的结果进行比较。
对于 20 例病例，CPS 时 PD-L1 的平均表达为 29.7（范围 0-101.5），TPS 时为 12.2（范围 0-95.8）；CPS 时 PD-L2 的平均表达为 7.9（范围 0-37.3），TPS 时为 1.9（范围 0-12.9）。95%的 OASC 检测到 PD-L1 CPS≥1，而 75%的 OASC 检测到 PD-L1 TPS≥1。PD-L2 CPS≥1 为 60%，而只有 20%的 PD-L2 TPS≥1。免疫细胞似乎对 PD-L1 和 PD-L2 的阳性表达有很大的贡献，并且大多数肿瘤中存在明显的 CD8 阳性 T 淋巴细胞浸润。PD-L1、PD-L2 和 CD8 的组织表达之间存在显著相关性。表达 PD-L1 水平较高的组织倾向于表达较高水平的 PD-L2 和 CD8。PD-L1 和 PD-L2 表达的程度也与免疫染色肿瘤的平方毫米面积相关，这表明肿瘤取样可能会影响眼附属器肿瘤中 PD-L1 和 PD-L2 表达的解释。
目前和以前的研究证实 PD-L1 和 PD-L2 在高比例的 OASCs 中表达。这些结果支持这样一个前提，即检查点抑制剂药物为 OASC 患者提供了相当大的治疗前景，并激发了临床试验的开展。
