Chiara Calabrese, Sofia Dellavalle, Chiara Spadazzi, Beate Sable, Dorothy French, Kumiko Isse, Khushboo Sharma, Vincenzo Laino, Roberto Fasano, Maria Maddalena Tumedei, Federica Pieri, Nicoletta Ranallo, Flavia Foca, Alessandro De Vita, Giacomo Miserocchi, Claudia Cocchi, Silvia Vanni, Sofia Gabellone, Oneda Cani, Giulia Sbanchi, Alberto Bongiovanni, Chiara Liverani
Given its high prevalence in extrapulmonary NECs, particularly those of GEP origin, it may have potential as a disease marker and therapeutic target in a clinical context where effective options are currently limited.
BACKGROUND: Neuroendocrine carcinomas (NECs) are rare and highly aggressive tumors, characterized by a dismal prognosis. Their underlying biology remains insufficiently understood, highlighting an urgent need for the identification of disease markers to enhance diagnostic and prognostic assessments, as well as to identify potential druggable targets. DLL3, an inhibitory regulator of the Notch signalling pathway, has emerged as a promising candidate in this context.
METHODS: We investigated DLL3 prevalence and pattern of expression in immunohistochemistry in NECs from multiple anatomical sites, with a focus on lung and gastroenteropancreatic (GEP) neoplasms.
RESULTS: DLL3 was found to be highly expressed in 68.8% of NECs overall, with the highest prevalence observed in GEP-NECs (85.7%). Immunohistochemical analysis revealed predominantly cytoplasmic localization, with a dot-like staining pattern particularly evident in gastrointestinal cases, suggestive of potential localization in neurosecretory granules. DLL3 levels did not significantly correlate with tumor proliferation index nor with overall survival. A correlation with chromogranin A expression was found.
CONCLUSIONS: Given its high prevalence in extrapulmonary NECs, particularly those of GEP origin, it may have potential as a disease marker and therapeutic target in a clinical context where effective options are currently limited.