Molecular characteristics of multifocal esophageal squamous cell carcinomas to discriminate multicentric origin from intramural metastasis

免疫系统 转移 CD8型 医学 食管 免疫疗法 病理 淋巴结 食管鳞状细胞癌 生物 癌症 免疫学 内科学
作者
Weihua Li,Na Cheng,Zitong Zhao,Bo Zheng,Zhaoyang Yang,Yang Xu,Yang Shao,Yongmei Song,Ning Lü,Liyan Xue
标识
DOI:10.1002/path.6010
摘要

Multifocal esophageal squamous cell carcinomas (ESCCs) can be diagnosed as of multicentric origin (MO) or intramural metastasis (IMM). We aimed here to accurately discriminate MO from IMM and explore the tumor immune microenvironment of multifocal ESCCs. Multifocal ESCCs were identified in 333 ESCC patients, and in 145 patients discrimination between MO and IMM was not possible by histopathological examination. Of the 145 patients, tissues of 14 were analyzed by whole-exome sequencing (WES) of 71 different tumor regions, and MO, IMM, and MO/IMM mixed groups were identified in three, ten, and one cases, respectively, based on the similarity of genomic architecture between or among different tumors from one patient. Further phylogenetic analyses revealed complex clonal evolution patterns in IMM cases, and tumor cells disseminated from the primary tumors to IMM tumors were independent of lymph node metastasis. The NanoString-based assay showed that immune cell infiltrates were significantly enriched, and that the immune and proliferation pathways were more activated, in large tumors than in small ones in MO but not IMM cases. Similarly, PD-L1 expression and the density of paratumoral CD8+ T cells were higher in large tumors than in small tumors in MO. Taken together, through analysis of the genomic and immune landscapes, our study has comprehensively characterized the heterogeneity and clonal relationship of multifocal ESCCs, which may be helpful in distinguishing MO from IMM, and for interpreting the immunotherapy responses for multifocal ESCC patients. © 2022 The Pathological Society of Great Britain and Ireland.
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