ArticleEndocrine pathology2025
DLL3 Expression in Neuroendocrine Carcinomas and Neuroendocrine Tumours: Insights From a Multicentric Cohort of 1294 Pulmonary and Extrapulmonary Neuroendocrine Neoplasms.
Article in Endocrine pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Clinicopathological Features of DLL3 Expression and T-Cell Infiltration in LCNEC: Insights From Pathology and Clinical Response to Tarlatamab.Thoracic cancer · 2026Article
- What are the Unmet Needs in Managing Digestive Neuroendocrine Carcinomas?Current oncology reports · 2026Review
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- DLL3-Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives.Drugs · 2026Review
- Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.JCO precision oncology · 2026Article
- Redefining the Role of Chemotherapy and Targeted Cytotoxic Delivery in Lung Neuroendocrine Tumors.Thoracic cancer · 2026Review
- Three-Tier Prognostic Stratification of Lung Carcinoids (NET G1-G2-G3) by Multivariable, Data-Driven Integration of Ki-67 and Mitotic Count.Endocrine pathology · 2026Article
- European Society of Neuroendocrine Tumors (ENETS) 2025 guidance paper for lung and thymic carcinoids.Journal of neuroendocrinology · 2026Article
- A translational colorectal cancer organoid biobank mirrors patients' tumor histology, molecular profiles, and treatment responses.Journal of experimental & clinical cancer research : CR · 2026Article
- MiNEN, amphicrine carcinomas, and conventional carcinomas with neuroendocrine differentiation: diagnostic criteria, open questions, and future perspectives.Virchows Archiv : an international journal of pathology · 2026Review
- DLL3 expression in neuroendocrine carcinomas: a comparative analysis across tumor origins.Frontiers in endocrinology · 2026Article
- Multi-center Assessment of DLL3 Expression by Immunohistochemistry in Medullary Thyroid Carcinoma.Endocrine pathology · 2025Article
- Review
- Delta-Like Ligand 3 Expression and Functional Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms.JCO precision oncology · 2025Article
- A bibliometric analysis of research trends and global perspectives on lung large cell neuroendocrine cancer.Journal of thoracic disease · 2025Article
- Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas.JCO precision oncology · 2025Article
- Expression of DLL3 and SEZ6 in the Spectrum of Neuroendocrine Neoplasia.Endocrine pathology · 2025Article
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Authors and funding
21 authors.
Funding
Abstract
Delta-like ligand 3 (DLL3) is frequently expressed in pulmonary small cell neuroendocrine carcinoma (SCNEC) and has emerged as a promising therapeutic target. However, limited data on DLL3 expression in other neuroendocrine neoplasms (NEN), such as extrapulmonary SCNEC, large cell neuroendocrine carcinomas (LCNEC), mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN), gastroenteropancreatic neuroendocrine tumours (GEP-NET), and pulmonary carcinoids, impedes an estimation if other types of NEN might be suitable candidates for anti-DLL3 therapies. We evaluated DLL3 expression in 1294 NEN and 479 non-neuroendocrine carcinomas, correlating the findings with histological subtypes, tumour localisation, and overall survival (OS). Furthermore, we explored the concordance of DLL3 expression during metastatic progression in 67 paired primary NEN and metastases. DLL3 expression was significantly higher in NEC (64.0%) compared to GEP-NET and pulmonary carcinoids (10.1%, p < 0.001), particularly in SCNEC (80.4%), followed by LCNEC (62.6%) and MiNEN (28.6%). DLL3 was common in pulmonary carcinoids (41.5%), but rare in GEP-NET (5.1%) and non-neuroendocrine carcinomas (1.3%). Overall DLL3 expression was highly concordant between metastases and corresponding primary NEN (92.5%, p < 0.001). In univariable analyses, DLL3-expressing pulmonary carcinoids (p = 0.005) and GEP-NET (p = 0.018) were associated with decreased OS, but this was not retained in multivariable analyses adjusting for stage and grade (p = n. s.). No prognostic impact was observed in pulmonary (p = 0.708) or GEP-NEC (p = 0.87). Our study highlights significant differences in DLL3 expression across NEN subtypes and localisations, with largely concordant expression in metastases. DLL3-based therapies may be effective in many NEC and pulmonary carcinoids, while DLL3 appears to be a minor therapeutic target for GEP-NET and non-neuroendocrine carcinomas.
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