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

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Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus
Lung Cancer ( IF 4.5 ) Pub Date : 2023-03-22 , DOI: 10.1016/j.lungcan.2023.107178
Yi-Jun Zhang ₁ , Si-Ping Xiong ₂ , Yuan-Zhong Yang ₁ , Sha Fu ₃ , Tong-Min Wang ₄ , David I Suster ₅ , Gui-Yang Jiang ₆ , Xiao-Fang Zhang ₇ , Jin Xiang ₁ , Yan-Xia Wu ₄ , Wen-Li Zhang ₄ , Yun Cao ₁ , Yu-Hua Huang ₁ , Jing-Ping Yun ₁ , Qian-Wen Liu ₈ , Qi Sun ₁ , Ya Chen ₂ , Xia Yang ₁ , Yan Li ₁ , En-Hua Wang ₆ , Jun-Ling Liu ₉ , Jiang-Bo Zhang ₄

Affiliation

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.
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; Department of Pathology, The Eighth Affiliated Hospital of Sun Yat-sen University, China.
Department of Pathology, Sun Yat-Sen Memorial Hospital, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China.
Department of Pathology, Immunology and Laboratory Medicine Rutgers University, New Jersey Medical School, USA.
Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, China.
Department of Pathology, Jiangxi Province Tumor Hospital, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China; Department of Thoracic, Sun Yat-Sen University Cancer Center, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China; Department of Internal Medicine, Sun Yat-sen University Cancer Center, China.

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.

中文翻译：

EBV 相关和 EBV 无关的低分化胸腺非角化鳞状细胞癌的临床病理特征、肿瘤免疫微环境和基因组景观

目标

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

材料和方法

这项多机构研究纳入了 85 名胸腺 PNDKSCC 患者。进行了 DNA 原位杂交以评估所有 85 个病例的 EBV 状态。进行免疫组织化学和下一代测序以比较 EBV 相关和 EBV 无关 PNDKSCC 之间临床病理学和分子特征的差异。肿瘤浸润淋巴细胞 (TIL) 也通过这些方法进行了分析。

结果

85例根据EBV状态分为EBV相关PDNKSCC 27例（31.8%）和EBV无关PDNKSCC 58例（68.2%），淋巴上皮瘤型（LP）35例（41.2%）和促纤维增生型（DP）50例（ 58.8 %）根据组织学特征。与 EBV 无关的 PDNKSCC 相比，EBV 相关的 PDNKSCC 患者年龄更小，并且更常见于 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）。这四个组显示与患者的 OS 和 PFS 显着相关。与 EBV 无关的 PNDKSCC 相比，EBV 相关的 PNDKSCC 具有显着更高的 PD-L1 + 肿瘤细胞 (TC) 以及 PD-L1 + 和 CD8 + 免疫细胞 (IC)。