Journal Article

Exploring the expression of DLL3 in gastroenteropancreatic neuroendocrine neoplasms and its potential diagnostic value

Wang, R., Hu, Y., Jiang, K., Zhang, L., Long, T., Li, J., Lu, M., Sun, Y., Wang, Z., Yin, L., Ma, X., Zhao, X.

2025

Overview

Delta-like protein (DLL3) is a novel therapeutic target. DLL3 expression in gastroenteropancreatic neuroendocrine tumors (GEP-NECs) is poorly understood, complicating the distinction between well-differentiated neuroendocrine tumors G3 (NET G3) and poorly differentiated NEC. DLL3 immunohistochemistry (IHC) was performed on 248 primary GEP-NECs, correlating with clinicopathological parameters, NE markers, PD-L1, Ki67 index, and prognosis. Achaete-scute complex-like 1 (ASCL1) IHC was performed on some GEP-NECs. DLL3 IHC was conducted on 36 GEP-NETs, 29 gastric adenocarcinomas (GACs), and metastatic tumors (9 lymph node metastases and 19 distant metastases). DLL3 expression rates were 54.8% in GEP-NECs at the primary site, associated with small cell neuroendocrine carcinoma (SCNEC) ( p  < 0.001), chemotherapy before baseline ( p  = 0.015), and at least two NE markers ( p  = 0.048). DLL3 expression in metastatic GEP-NECs was similar to that of primary tumors. Expression rates in NET G1, NET G2, NET G3, and GACs were 0%, 0%, 15.8%, and 0%, respectively, highlighting DLL3 as a powerful tool for identifying poorly differentiated NEC. DLL3 expression was related to ASCL1 in GEP-NECs, especially in SCNEC. It was not correlated with progression-free survival (PFS) or overall survival(OS), regardless of cutoff value (1%, 50%, 75%). In conclusion, DLL3 targeted therapy may offer potential for the treatment of poorly differentiated NEC of the digestive system, although further studies are needed to validate its efficacy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/67 / 692/163 / 692/4020 / 692/53 / Adult / Aged / Aged, 80 and over / ASCL1 / ASCL1 protein / Biomarkers, Tumor - metabolism / Chemotherapy / Delta-like protein / Digestive system / Female / Gastroenteropancreatic neuroendocrine tumors / Humanities and Social Sciences / Humans / Immunohistochemistry / Intestinal Neoplasms - diagnosis / Intestinal Neoplasms - metabolism / Intestinal Neoplasms - pathology / Intracellular Signaling Peptides and Proteins - genetics / Intracellular Signaling Peptides and Proteins - metabolism / Lymph nodes / Male / Medical prognosis / Membrane Proteins - genetics / Membrane Proteins - metabolism / Metastases / Metastasis / Middle Aged / multidisciplinary / Neuroendocrine tumors / Neuroendocrine Tumors - diagnosis / Neuroendocrine Tumors - metabolism / Neuroendocrine Tumors - mortality / Neuroendocrine Tumors - pathology / Pancreatic Neoplasms - diagnosis / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - mortality / Pancreatic Neoplasms - pathology / PD-L1 protein / Prognosis / Science / Science (multidisciplinary) / Stomach Neoplasms - diagnosis / Stomach Neoplasms - metabolism / Stomach Neoplasms - mortality / Stomach Neoplasms - pathology / Therapeutic target / Therapeutic targets / Tumors