2023 World Conference on Lung Cancer (Posters)-P2.13. Spatiotemporal Heterogeneity of Transcription Factor-Based Subtype Assignment in Small Cell Lung Carcinoma

P2.13. Spatiotemporal Heterogeneity of Transcription Factor-Based Subtype Assignment in Small Cell Lung Carcinoma - PDF(Abstract)

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This study investigated the spatiotemporal heterogeneity of transcription factor-based subtype assignment in small cell lung carcinoma (SCLC). SCLC can be classified into subtypes (ASCL1, NEUROD1, and POU2F3) with specific therapeutic vulnerabilities. The researchers examined whether these subtypes vary over time and different locations within a patient.<br /><br />The researchers analyzed formalin-fixed paraffin-embedded samples from 84 SCLC patients at multiple sites or time points. Immunohistochemistry was performed for ASCL1, NEUROD1, and POU2F3, and subtype assignment was based on the highest H score. <br /><br />Out of 179 samples, 55% were ASCL1-dominant, 28% were NEUROD1-dominant, 8% were POU2F3-dominant, 1% were ASCL1-NEUROD1 co-dominant, and 7% were triple-negative. Among the lung tumors, 63% were ASCL1-dominant, while among extrapulmonary samples, including lymph nodes, 50% were ASCL1-dominant. <br /><br />For patients with only two samples available for comparison, 77% had concordant subtypes, while 23% had discordant subtypes. When accounting for double expression of ASCL1 and NEUROD1, 14.9% of patients with two samples had discordant subtypes. No significant differences in discordance rates were found based on location or time intervals between samples. <br /><br />The study concluded that while most patients had concordant subtype assignments, 15% displayed discordant subtypes. These findings highlight the spatiotemporal heterogeneity of SCLC in clinical samples, which has implications for the use of subtype-specific therapies. <br /><br />The provided document includes a representative image of concordant and discordant biopsies for NEUROD1 and POU2F3 versus ASCL1-dominant SCLC. This research contributes to the understanding of SCLC subtypes and underscores the importance of considering tumor heterogeneity in treatment strategies.

Asset Subtitle

Mari Mino-Kenudson

Meta Tag

Speaker Mari Mino-Kenudson

Topic SCLC & Neuroendocrine Tumors: Biomarkers & Radiomics

Keywords

transcription factor-based subtype assignment

small cell lung carcinoma

SCLC

ASCL1

NEUROD1

POU2F3

spatiotemporal heterogeneity

concordant subtypes

discordant subtypes

tumor heterogeneity