胃神经内分泌癌（NEC）是一种罕见的癌症，具有高度侵袭性。尽管三级淋巴结构（TLS）是各种癌症中众所周知的预后因素，但它们在胃 NEC 中的作用仍未被探索。已发现肺部 NEC 的独特免疫组织化学亚型，然而，其在胃 NEC 中的可行性尚不清楚。在 48 个手术切除的胃 NEC 中评估了 TLS（淋巴聚集体、初级和次级滤泡）的存在和成熟，并与免疫组织化学亚型进行比较，使用一组 ASCL1、NeuroD1、POU2F3、YAP1 和 DLL3 以及三种神经内分泌 (NE) 标记物。具有次级卵泡的患者的总生存期 (OS) 和无复发生存期 (RFS；两者，p = 0.004) 明显优于那些患者没有他们。根据层次聚类，胃 NEC 被分为所有低/阴性（31%）、高 YAP1（19%）、高 DLL3/低 NE（29%）和高 NE（21%）表达组。高 DLL3/低 NE 组与缺乏 TLS 相关 (p = 0.026)，并表现出最差的 OS (p = 0.026)。远处转移和缺乏次级滤泡是 OS 和 RFS 的不良独立预后因素。TLS 的评估是胃 NEC 的可行且有效的生物标志物，从而实现更好的预后和更有效的免疫治疗。此外，胃 NEC 可分为四个免疫组织化学上不同的组，其中高 DLL3/低 NE 组的 OS 最差，缺乏 TLS。© 2024。作者获得国际胃癌协会独家许可和日本胃癌协会。

Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown.The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers.Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS.The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and more effective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.