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Expression patterns, prognostic value, and intratumoral heterogeneity of PD-L1 and PD-1 in thymoma and thymic carcinoma
Journal of Thoracic Oncology ( IF 20.4 ) Pub Date : 2018-04-24
Dwight Owen, Benjamin Chu, Amy M. Lehman, Lakshmanan Annamalai, Jennifer H. Yearley, Konstantin Shilo, Gregory A. Otterson

Introduction

Thymic epithelial tumors (TET) including thymoma and thymic carcinoma are rare tumors with little data available to guide treatment. Immunotherapy with checkpoint blockade has shown promising activity, but data regarding the expression patterns and prognostic implications of programmed death 1 (PD-1) and its ligand (PD-L1) in TET have yielded conflicting results. Intratumoral heterogeneity of PD-1/L1 expression has been demonstrated in other cancers but has not been described in the TET literature.

Methods

We performed a retrospective single-center review of 35 patients with resected TET. PD-1/L1 expression was assessed by immunohistochemistry utilizing PD-1 clone: NAT105 and PD-L1 clone: 22C3. Tumor samples from 35 patients were evaluated including 32 patients with thymoma and 3 patients with thymic carcinoma.

Results

PD-L1 expression was detected in 83% (29/35) tumor samples, including 100% (3/3) of thymic carcinoma patients and 81% (26/32) of thymoma patients. PD-1 expression was detected in 77% (27/35), including 33% (1/3) of thymic carcinoma patients and 81% (26/32) thymoma patients. High PD-1 expression was associated with lower grade tumors. Unlike prior studies, PD-L1 expression was not associated with higher grade tumors or higher stage. Neither PD-L1 nor PD-1 expression was significantly associated with survival. Three patients with thymoma had multiple tumor sections evaluated for expression of PD-1/L1, with differing expression patterns of both PD-L1 and PD-1 observed in two patients.

Conclusions

This study confirms high expression of PD-L1 and PD-1 in TET and demonstrates for the first time intra-tumoral heterogeneity of PD-L1 and PD-1 in thymoma patients.



中文翻译:

PD-L1和PD-1在胸腺瘤和胸腺癌中的表达模式,预后价值和瘤内异质性

介绍

胸腺上皮肿瘤(TET)包括胸腺瘤和胸腺癌是罕见的肿瘤,几乎没有可用于指导治疗的数据。具有检查点封锁的免疫疗法已显示出令人鼓舞的活性,但有关TET中程序性死亡1(PD-1)及其配体(PD-L1)的表达模式和预后影响的数据产生了矛盾的结果。PD-1 / L1表达的肿瘤内异质性已在其他癌症中得到证实,但尚未在TET文献中进行描述。

方法

我们对35例TET切除患者进行了回顾性单中心回顾。通过使用PD-1克隆:NAT105和PD-L1克隆:22C3的免疫组织化学评估PD-1 / L1表达。对35例患者的肿瘤样本进行了评估,其中包括32例胸腺瘤患者和3例胸腺癌患者。

结果

在83%(29/35)的肿瘤样本中检测到PD-L1表达,包括100%(3/3)的胸腺癌患者和81%(26/32)的胸腺瘤患者。在77%(27/35),包括33%(1/3)的胸腺癌患者和81%(26/32)胸腺瘤患者中检测到PD-1表达。高PD-1表达与较低级别的肿瘤有关。与先前的研究不同,PD-L1的表达与更高级别的肿瘤或更高的分期无关。PD-L1和PD-1的表达均与生存率无关。三名胸腺瘤患者的多个肿瘤切片评估了PD-1 / L1的表达,其中两名患者观察到PD-L1和PD-1的表达模式不同。

结论

这项研究证实了TET中PD-L1和PD-1的高表达,并首次证明了胸腺瘤患者PD-L1和PD-1的肿瘤内异质性。

更新日期:2018-04-25
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