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胸腺癌中 PD-L1/PD-1 的表达。

Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus.

机构信息

Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Medical College of Wisconsin, Milwaukee, WI, USA.

出版信息

Mod Pathol. 2018 Dec;31(12):1801-1806. doi: 10.1038/s41379-018-0097-4. Epub 2018 Jul 4.

Abstract

Poorly differentiated non-keratinizing squamous cell carcinoma of the thymus, also known as lymphoepithelioma-like carcinoma, is a rare primary malignant neoplasm of thymic origin. The mainstay of treatment for these tumors is surgical and they tend to respond poorly to chemotherapy. The checkpoint programmed cell death ligand-1 protein (PD-L1) bound to its receptor (PD-1) has been demonstrated to be an important therapeutic target for many different tumors. Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus may indicate that these tumors are potential targets for inhibitor therapy. Twenty-one cases of lymphoepithelioma-like carcinoma of the thymus were collected and reviewed. Tissue microarrays were created using triplicate 2 mm cores for each case. PD-L1/PD-1 staining pattern (neoplastic cells versus tumor infiltrating lymphocytes) was documented for each case. Out of 21 cases, 15 (71.4%) showed various degrees of membranous PD-L1 staining. Of the positive cases, 48% showed high expression of PD-L1 (>50% of tumor cells) and 24% showed low expression (<50%). PD-1 staining showed focal positivity in 12/20 (60%) cases among tumor infiltrating lymphocytes. PD-L1/PD-1 inhibitor therapy has been applied successfully in other solid malignant tumors with high expression of PD-L1/PD-1. The high level of PD-L1 expression in our cases indicates that PD-L1 may play a role in the pathogenesis of these tumors and that PD-L1/PD-1 blockade may be a viable therapeutic option for patients with lymphoepithelioma-like carcinoma of the thymus who have failed other first-line therapies.

摘要

胸腺低分化非角化性鳞状细胞癌,又称淋巴上皮样癌,是一种罕见的胸腺原发性恶性肿瘤。这些肿瘤的主要治疗方法是手术,且对化疗的反应较差。已证实细胞程序性死亡配体 1 蛋白(PD-L1)与受体(PD-1)结合是许多不同肿瘤的重要治疗靶点。胸腺癌中的 PD-L1/PD-1 的表达可能表明这些肿瘤是抑制剂治疗的潜在靶点。收集并回顾了 21 例胸腺癌。为每个病例创建了组织微阵列,每个病例使用 3 个 2mm 核心的重复进行。记录了每个病例的 PD-L1/PD-1 染色模式(肿瘤细胞与肿瘤浸润淋巴细胞)。在 21 例中,有 15 例(71.4%)显示出不同程度的膜 PD-L1 染色。在阳性病例中,48%显示 PD-L1 高表达(>50%的肿瘤细胞),24%显示低表达(<50%)。PD-1 染色显示肿瘤浸润淋巴细胞中有 12/20(60%)例存在局灶性阳性。PD-L1/PD-1 抑制剂治疗已成功应用于其他 PD-L1/PD-1 高表达的实体恶性肿瘤。我们的病例中 PD-L1 表达水平较高,这表明 PD-L1 可能在这些肿瘤的发病机制中起作用,并且 PD-L1/PD-1 阻断可能是其他一线治疗失败的胸腺癌患者的一种可行的治疗选择。

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