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

Yi-Jun Zhang; Si-Ping Xiong; Yuan-Zhong Yang; Sha Fu; Tong-Min Wang; David I Suster; Gui-Yang Jiang; Xiao-Fang Zhang; Jin Xiang; Yan-Xia Wu; Wen-Li Zhang; Yun Cao; Yu-Hua Huang; Jing-Ping Yun; Qian-Wen Liu; Qi Sun; Ya Chen; Xia Yang; Yan Li; En-Hua Wang; Jun-Ling Liu; Jiang-Bo Zhang

doi:10.1016/j.lungcan.2023.107178

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. 2023 May:179:107178. doi: 10.1016/j.lungcan.2023.107178. Epub 2023 Mar 22.

Authors

Yi-Jun Zhang¹, Si-Ping Xiong², Yuan-Zhong Yang¹, Sha Fu³, Tong-Min Wang⁴, David I Suster⁵, Gui-Yang Jiang⁶, Xiao-Fang Zhang⁷, Jin Xiang¹, Yan-Xia Wu⁴, Wen-Li Zhang⁴, Yun Cao¹, Yu-Hua Huang¹, Jing-Ping Yun¹, Qian-Wen Liu⁸, Qi Sun¹, Ya Chen², Xia Yang¹, Yan Li¹, En-Hua Wang⁹, Jun-Ling Liu¹⁰, Jiang-Bo Zhang¹¹

Affiliations

¹ 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.
² 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.
³ Department of Pathology, Sun Yat-Sen Memorial Hospital, China.
⁴ Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China.
⁵ Department of Pathology, Immunology and Laboratory Medicine Rutgers University, New Jersey Medical School, USA.
⁶ Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, China.
⁷ Department of Pathology, Jiangxi Province Tumor Hospital, China.
⁸ 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.
⁹ Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, China. Electronic address: wangeh@hotmail.com.
¹⁰ 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. Electronic address: liujl@sysucc.org.cn.
¹¹ 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.

PMID: 37004385
DOI: 10.1016/j.lungcan.2023.107178

Abstract

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.

Keywords: EBV; Genomic landscape; Immunotherapy; Poorly differentiated nonkeratinizing squamous cell carcinoma; Thymus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen / metabolism
Carcinoma, Squamous Cell* / pathology
Genomics
Herpesvirus 4, Human / metabolism
Humans
Lung Neoplasms* / pathology
Lymphocytes, Tumor-Infiltrating
Prognosis
Tumor Microenvironment

Substances

B7-H1 Antigen