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EBV 相关及 EBV 无关的胸腺低分化非角化性鳞状细胞癌的临床病理特征、肿瘤免疫微环境及基因组图谱

英文原题：Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.

查看英文原题

Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.

PubMed 2023/03/22（内容时间） Lung Cancer Q1 · IF 5.3（JCR 2025）

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肺癌地区：中国
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研究概要

EBV 相关的 PDNKSCC，尤其是第 1 组，可能成为免疫治疗的候选对象，且 EBV 阳性可能因其高肿瘤突变负荷而为靶向治疗的选择提供指征。

研究思路结论见上方概要

目的

关于胸腺EBV相关的低分化非角化性鳞状细胞癌（PDNKSCC），也称为淋巴上皮癌（LEC），由于其罕见性，相关知识极为有限。

方法

这项多机构研究纳入了85例胸腺PDNKSCC患者。对所有85例病例进行DNA原位杂交以评估EBV状态。采用免疫组织化学和下一代测序比较EBV相关与EBV无关PDNKSCC在临床病理和分子特征上的差异。还通过这些方法对TIL（肿瘤浸润淋巴细胞）（TILs）进行了分析。

结果

85例病例根据EBV状态分为27例EBV相关PDNKSCC（31.8 %）和58例EBV无关PDNKSCC（68.2 %），根据组织学特征分为35例淋巴上皮瘤样型（LP）（41.2 %）和50例促纤维增生型（DP）（58.8 %）。与EBV无关PDNKSCC相比，EBV相关PDNKSCC表现出更年轻的患者优势和更常见的LP亚型。此外，LP型病例分为两组：第1组（EBV相关，20/85）和第2组（EBV无关，15/85）；DP型病例分为第3组（EBV无关，43/85）和第4组（EBV相关，7/85）。四组与患者的OS和PFS显著相关。EBV相关PDNKSCC的PD-L1 +肿瘤细胞（TCs）以及PD-L1 +和CD8 +免疫细胞（ICs）显著高于EBV无关PDNKSCC。肿瘤微环境免疫分型（TMIT）I（PDL1-Tumor+/CD8-High）在EBV相关PDNKSCC中更常见，尤其是在第1组（LP且EBV相关）中，超过90 %的病例属于TMIT I。分子分析表明，EBV相关PDNKSCC的肿瘤突变负荷和体细胞突变频率显著高于EBV无关病例。

展开英文摘要原文
OBJECTIVES

Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity.

MATERIALS AND METHODS

This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods.

RESULTS

The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases.

CONCLUSIONS

EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.

论文信息

作者
Zhang YJ、Xiong SP、Yang YZ、Fu S、Wang TM、Suster DI、Jiang GY、Zhang XF
第一作者单位
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China; Department of Pathology, Sun Yat-Sen University Cancer Center, China.China
通讯作者单位
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China. Electronic address: zhangjb@sysucc.org.cn.China
文献类型
非美国政府资助研究
期刊
Lung cancer (Amsterdam, Netherlands)2023 May
原文标识
PubMed 37004385　·　DOI 10.1016/j.lungcan.2023.107178

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