2025 Hot Topic in Basic & Translational Science: Small Cell Lung Cancer - Posters-PP01.10 ASCL1 and NEUROD1 are Highly Specific Markers of Lung vs Digestive Carcinoids/Neuroendocrine Tumors

PP01.10 ASCL1 and NEUROD1 are Highly Specific Markers of Lung vs Digestive Carcinoids/Neuroendocrine Tumors

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This study explores the expression of specific transcriptional markers in lung carcinoids and digestive neuroendocrine tumors (NETs) to better define their diagnostic differentiation. It highlights the use of ASCL1 and NEUROD1 as highly specific markers for distinguishing between lung and digestive NETs, respectively. <br /><br />Findings showed that ASCL1 was expressed in 50.5% of lung carcinoids but only in 0.5% of digestive NETs, whereas NEUROD1 was absent in lung carcinoids but present in 52% of pancreatic NETs (Pan-NETs) and 39% of small intestine NETs (SI-NETs). OTP, another marker, was positive in 83% of lung carcinoids compared to a mere 0.5% of digestive NETs, reinforcing the distinct expression patterns between the lung and digestive systems. TTF-1 was positive in 32.5% of lung carcinoids but was absent in digestive NETs.<br /><br />Additionally, DLL3 was found positive in 50% of lung carcinoids and correlated moderately with ASCL1, but it was only detected in 4% of pancreatic NETs and not at all in small intestinal NETs. The absence of YAP1 and POU2F3 expression in both lung carcinoids and digestive NETs was also noted.<br /><br />These results suggest that ASCL1 and NEUROD1 can help diagnose NETs of unknown primary origin, as lung carcinoids often show positivity for ASCL1 even when negative for OTP and TTF-1, which are traditionally used markers. The study also supports the potential for targeted therapies, particularly DLL3, in lung carcinoids. These findings emphasize the biological and diagnostic differences between lung and digestive tract NETs, expanding the knowledge base for better NET classification and treatment strategies.

Asset Subtitle

Jonathan Willner

Keywords

lung carcinoids

digestive neuroendocrine tumors

ASCL1

NEUROD1

diagnostic differentiation

transcriptional markers

OTP

TTF-1

DLL3

targeted therapies