Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins

Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete-scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/ NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.

Palavras-chave

Large-cell neuroendocrine carcinomas, Small-cell lung carcinomas, Immunohistochemistry, Digital analysis, Transmission electron microscopy, DLL3/ASCL1

URI

https://observatorio.fm.usp.br/handle/OPI/58051

Referências

Amin MB, 2017, CA-CANCER J CLIN, V67, P93, DOI 10.3322/caac.21388
Asamura H, 2006, J CLIN ONCOL, V24, P70, DOI 10.1200/JCO.2005.04.1202
Bankhead P, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-17204-5
Borges M, 1997, NATURE, V386, P852, DOI 10.1038/386852a0
Collier JR, 1996, J THEOR BIOL, V183, P429, DOI 10.1006/jtbi.1996.0233
Fasano M, 2015, J THORAC ONCOL, V10, P1133, DOI 10.1097/JTO.0000000000000589
George J, 2018, NAT COMMUN, V9, DOI 10.1038/s41467-018-03099-x
Hermans BCM, 2019, LUNG CANCER, V138, P102, DOI 10.1016/j.lungcan.2019.10.010
Kim JW, 2022, ISCIENCE, V25, DOI 10.1016/j.isci.2022.105603
Meder L, 2016, INT J CANCER, V138, P927, DOI 10.1002/ijc.29835
Morimoto M, 2012, DEVELOPMENT, V139, P4365, DOI 10.1242/dev.083840
Nelson BR, 2009, DEV DYNAM, V238, P2163, DOI 10.1002/dvdy.21848
Nicholson AG, 2022, J THORAC ONCOL, V17, P362, DOI 10.1016/j.jtho.2021.11.003
Owen DH, 2019, J HEMATOL ONCOL, V12, DOI 10.1186/s13045-019-0745-2
Rojo F, 2020, LUNG CANCER, V147, P237, DOI 10.1016/j.lungcan.2020.07.026
Rudin CM, 2017, LANCET ONCOL, V18, P42, DOI [10.1016/s1470-2045(16)30565-4, 10.1016/S1470-2045(16)30565-4]
Rudin CM, 2023, J HEMATOL ONCOL, V16, DOI 10.1186/s13045-023-01464-y
Sutherland KD, 2011, CANCER CELL, V19, P754, DOI 10.1016/j.ccr.2011.04.019
Tendler S, 2020, PLOS ONE, V15, DOI 10.1371/journal.pone.0240973
Yao J, 2022, ONCOLOGIST, V27, P940, DOI 10.1093/oncolo/oyac161

Coleções

Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/09
Artigos e Materiais de Revistas Científicas - ODS/03

Página do item completo