812 PROGRAMMED CELL DEATH PROTEIN 1/PROGRAMMED DEATH LIGAND 1 AND HLA-CLASS I ARE POTENTIAL THERAPEUTIC TARGETS IN ESOPHAGEAL NEUROENDOCRINE CARCINOMA

Abstract

Abstract Esophageal neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. Pembrolizumab was recommended for the treatment of PD-L1 positive tumors in esophageal cancer and the combined positive score (CPS) was reported to be a better predictor of efficacy compared to the tumor proportion score (TPS). We investigated the expression profile of potential therapeutic targets (PD-L1, HLA class I, Mismatch repair (MMR) proteins) and tumor infiltrating lymphocytes (TILs) in esophageal NEC. Methods 15 NECs of the esophagus including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma (SCC) component were investigated in the study. The expression of PD-L1 (quantitatively evaluated by CPS and TPS), HLA class I, and MMR protein expression were examined immunohistochemically. TIL abundance was examined semiquantitatively by observation of H&E slides. Results Nine (60%) showed a CPS ≥ 1, five (33%) showed a CPS ≥10, and five cases showed a TPS ≥1. Survival analysis showed a significantly longer overall survival in the CPS ≥1 group than in the CPS <1 group. Deficiency of MMR protein was not observed in any cases. HLA-Class I expression was retained in 10 (67%), and loss of HLA-Class I was significantly correlated with frequent lymph node metastasis, high TNM Stage, and low TIL. Three showed both PD-L1 CPS ≥ 10 and high TIL. Conclusion In esophageal NEC, PD-L1 positivity and preserved HLA-Class I expression were frequently observed, and PD-L1 CPS ≥ 1 was significantly associated with the better prognosis of esophageal NEC. Therefore, the PD-1/PD-L1 pathway and HLA-class I are thought to be potential therapeutic targets in esophageal neuroendocrine carcinoma.