Comprehensive genomic profiling and PD-L1 expression of primary lymphoepithelioma-like carcinoma of the stomach and parotid gland.

BACKGROUND

To investigate the comprehensive genomic profiling and programmed cell death ligand-1 (PD-L1) expression of primary lymphoepithelioma-like carcinoma (LELC) of different anatomical sites in the Chinese population and explore potential therapeutic strategies.

METHODS

Capture-based targeted sequencing was performed on tumor tissue samples collected from 35 patients with LELC. Tumor tissues were stained by immunohistochemistry (IHC) for PD-L1. The molecular features of LELC of the stomach/parotid gland and associations between somatic alterations and survival outcomes in LELC of the stomach were explored.

RESULTS

All patients with LELC of the stomach/parotid gland were microsatellite-stable with Epstein-Barr virus infection. A total of 215 somatic alterations spanning 126 genes were identified from 18 patients with LELC of the stomach. The most frequently mutated genes included , , , and . In addition, 37 somatic alterations spanning 30 genes were identified from seven patients with LELC of the parotid gland. , , and were the most frequently mutated genes. All cases of LELC of the stomach/parotid gland had a low tumor mutational burden (TMB) level, but a high PD-L1 expression level. Compared with LELC of the parotid gland, LELC of the stomach had a significantly higher TMB (1.0 5.0 mutations/Mb, P=0.0047) and a lower PD-L1 expression level (combined positive score: 90.0 47.5, P=0.0058). In addition, the presence of alterations in the p53 signaling pathway, homologous recombination pathway, and deoxyribonucleic acid (DNA) damage response pathway predicted unfavorable overall survival in patients with LELC of the stomach.

CONCLUSIONS

This study is the first to elucidate the comprehensive genomic profiling of LELC of the stomach in the Chinese population, and the first to demonstrate the molecular features of LELC of the parotid gland. The detection of high PD-L1 expression raises the potential of checkpoint immunotherapy for LELC of the stomach/parotid gland.

KEYWORDS

Lymphoepithelioma-like carcinoma of the stomach (LELC of the stomach), lymphoepithelioma-like carcinoma of the parotid gland (LELC of the parotid gland), programmed cell death ligand-1 (PD-L1), genomic profiling, immunotherapy.