Prognostic Significance of Tertiary Lymphoid Structures in Gastric Neuroendocrine Carcinoma with Association to Delta-like Ligand 3 and Neuroendocrine Expressions

Overview

Journal Gastric Cancer

Specialties Gastroenterology
Oncology

Date 2024 Oct 1

PMID 39352632

Authors

Bokyung Ahn

Deokhoon Kim

Mi-Ju Kim

Seo-Rin Jeong

In Hye Song

Joo Young Kim

Soon Auck Hong

Sun-Young Jun

HyungJun Cho

Young Soo Park

Freddy E Escorcia

Joon-Yong Chung

Seung-Mo Hong

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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