Zhang Long, Yu Boyao, Liu Zhichao, Wei Jinzhi, Pan Jie, Jiang Chao, Li Zhigang
Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Cancers (Basel). 2023 Mar 13;15(6):1732. doi: 10.3390/cancers15061732.
Esophageal neuroendocrine neoplasms (E-NENs) are a rare and poorly reported subtype of esophageal carcinoma. We analyzed the differences in clinicopathological features, prognosis, and tumor-infiltrating lymphocytes (TILs) between E-NENs and esophageal squamous cell carcinoma (ESCC).
A total of 3620 patients who underwent esophagectomy were enrolled retrospectively. The study cohort was divided into two groups (E-NENs and ESCC) through propensity-score matching, and the prognosis and TILs were compared between the two groups. The TILs were assessed using tumor specimens (including six cases of ESCC, six cases of neuroendocrine carcinomas [NECs], and six cases of mixed neuroendocrine-non-neuroendocrine neoplasms [MiNENs]).
E-NENs accounted for 3.0% (107/3620) of cases, among which there were just 3 neuroendocrine tumor cases, 51 NEC cases, and 53 MiNENs cases. After matching, esophageal neuroendocrine carcinomas (E-NECs) showed both poorer 5-year overall survival (OS; 35.4% vs. 54.8%, = 0.0019) and recurrence-free survival (RFS; 29.3% vs. 48.9%, < 0.001) compared with ESCC. However, the differences were not prominent in the subgroup with stage I. No significant survival benefit was observed for E-NECs with multimodal therapy. Multivariate analysis demonstrated that E-NECs are an independent risk factor for OS and RFS. In the exploratory analysis, E-NECs were associated with less infiltration of immune cells compared with ESCC.
E-NECs are significantly associated with a poorer prognosis than ESCC except for early-stage disease. The fewer TILs within the tumor microenvironment of E-NECs compared with ESCC results in weaker anti-tumor immunity and may lead to a poorer prognosis.
食管神经内分泌肿瘤（E-NENs）是食管癌中一种罕见且报道较少的亚型。我们分析了E-NENs与食管鳞状细胞癌（ESCC）在临床病理特征、预后及肿瘤浸润淋巴细胞（TILs）方面的差异。
回顾性纳入3620例行食管切除术的患者。通过倾向得分匹配将研究队列分为两组（E-NENs组和ESCC组），比较两组的预后及TILs。使用肿瘤标本（包括6例ESCC、6例神经内分泌癌[NECs]和6例神经内分泌-非神经内分泌混合肿瘤[MiNENs]）评估TILs。
E-NENs占病例的3.0%（107/3620），其中神经内分泌肿瘤病例仅3例，NEC病例51例，MiNENs病例53例。匹配后，食管神经内分泌癌（E-NECs）与ESCC相比，5年总生存率（OS；35.4%对54.8%，P = 0.0019）和无复发生存率（RFS；29.3%对48.9%，P < 0.001）均较差。然而，在I期亚组中差异不显著。多模式治疗对E-NECs未观察到显著的生存获益。多因素分析表明，E-NECs是OS和RFS的独立危险因素。在探索性分析中，与ESCC相比，E-NECs与免疫细胞浸润较少相关。
除早期疾病外，E-NECs与比ESCC更差的预后显著相关。与ESCC相比，E-NECs肿瘤微环境中TILs较少导致抗肿瘤免疫较弱，可能导致预后较差。
