Schmitt, Maxime and Bohnenberger, Hanibal and Bartsch, Detlef Klaus and Wagner, Daniel-Christoph and Litmeyer, Anne-Sophie and Grass, Albert and Rinke, Anja and Koch, Christine and Kremer, Marcus and Evert, Matthias and Maerkl, Bruno and Quaas, Alexander and Eckstein, Markus and Steinestel, Konrad and Denkert, Carsten and Steiger, Katja and Kloeppel, Guenter and Kasajima, Atsuko and Tschurtschenthaler, Markus and Foersch, Sebastian and Jesinghaus, Moritz (2025) DLL3 Expression in Neuroendocrine Carcinomas and Neuroendocrine Tumours: Insights From a Multicentric Cohort of 1294 Pulmonary and Extrapulmonary Neuroendocrine Neoplasms. ENDOCRINE PATHOLOGY, 36 (1): 9. ISSN 1046-3976, 1559-0097
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DELTA-LIKE PROTEIN-3; CLASSIFICATION; IRS; DLL3; Neuroendocrine neoplasms; Neuroendocrine tumour; Neuroendocrine carcinoma |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2026 09:38 |
| Last Modified: | 17 Apr 2026 09:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67698 |
Actions (login required)
 |
View Item |
