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@ARTICLE{Schmitt:300176,
      author       = {M. Schmitt and H. Bohnenberger and D. K. Bartsch and D.-C.
                      Wagner and A.-S. Litmeyer and A. Grass and A. Rinke and C.
                      Koch and M. Kremer and M. Evert and B. Märkl and A. Quaas
                      and M. Eckstein and K. Steinestel and C. Denkert and K.
                      Steiger and G. Klöppel and A. Kasajima and M.
                      Tschurtschenthaler$^*$ and S. Foersch and M. Jesinghaus},
      title        = {{DLL}3 {E}xpression in {N}euroendocrine {C}arcinomas and
                      {N}euroendocrine {T}umours: {I}nsights {F}rom a
                      {M}ulticentric {C}ohort of 1294 {P}ulmonary and
                      {E}xtrapulmonary {N}euroendocrine {N}eoplasms.},
      journal      = {Endocrine pathology},
      volume       = {36},
      number       = {1},
      issn         = {1046-3976},
      address      = {New York, NY},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-00653},
      pages        = {9},
      year         = {2025},
      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.},
      keywords     = {Humans / Neuroendocrine Tumors: pathology / Neuroendocrine
                      Tumors: metabolism / Neuroendocrine Tumors: mortality /
                      Carcinoma, Neuroendocrine: pathology / Carcinoma,
                      Neuroendocrine: metabolism / Carcinoma, Neuroendocrine:
                      mortality / Lung Neoplasms: pathology / Lung Neoplasms:
                      metabolism / Male / Female / Intracellular Signaling
                      Peptides and Proteins: metabolism / Intracellular Signaling
                      Peptides and Proteins: biosynthesis / Middle Aged / Aged /
                      Membrane Proteins: metabolism / Membrane Proteins:
                      biosynthesis / Biomarkers, Tumor: analysis / Biomarkers,
                      Tumor: metabolism / Adult / Cohort Studies / Aged, 80 and
                      over / DLL3 (Other) / Neuroendocrine carcinoma (Other) /
                      Neuroendocrine neoplasms (Other) / Neuroendocrine tumour
                      (Other) / DLL3 protein, human (NLM Chemicals) /
                      Intracellular Signaling Peptides and Proteins (NLM
                      Chemicals) / Membrane Proteins (NLM Chemicals) / Biomarkers,
                      Tumor (NLM Chemicals)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40153138},
      doi          = {10.1007/s12022-025-09854-3},
      url          = {https://inrepo02.dkfz.de/record/300176},
}