Tumor‐infiltrating lymphocytes‐based subtypes and genomic characteristics of EBV‐associated lymphoepithelioma‐like carcinoma

Abstract

Tumor‐infiltrating lymphocytes (TILs) offer a key for morphological diagnosis of lymphoepithelioma‐like carcinoma (LELC) and are the foundation of oncoimmunology. To date, no reports have found a specific risk stratification value of TILs and related it to genomic variation in LELC. Based on the stromal TILs (str‐TILs) ratio, we classified 105 Epstein–Barr virus (EBV)‐associated LELC cases into two subtypes: patients with ≥60% str‐TILs area ratio in tumor were classified as subtype I, and otherwise as subtype II. Subtype I patients had significantly better progression‐free survival (PFS) and overall survival (OS). We also explored the genomic characteristics of EBV‐associated LELC within different involved organs. We performed whole‐exome sequencing for 51 patients with enough tissue and analyzed the genomic characteristics of EBV‐associated LELC. Overall, EBV‐associated LELCs were characterized by a low somatic mutation rate and copy number variations; the enriched genetic lesions affected RTK‐RAS, PI3K, and cell cycle pathways. Moreover, EBV‐associated LELCs from different organs were more similar to each other genetically as compared with other traditional carcinomas of the same sites―as evidenced by unsupervised clustering based on the quantitative data from both mutation signature and chromosomal aneuploidies. Notably, EBV‐associated LELC patients with oncogenic driver alterations showed a worse prognosis compared with patients without such alterations. © 2022 The Pathological Society of Great Britain and Ireland.