WCLC 2025 - Posters & ePosters-EP.06.16 Immunophenotyping of the Molecular Subtypes of Small Cell Lung Cancer and Its Correlation With Prognostic and Therapeutic Implications

EP.06.16 Immunophenotyping of the Molecular Subtypes of Small Cell Lung Cancer and Its Correlation With Prognostic and Therapeutic Implications

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This study, presented by Dr. Sunil Pasricha and colleagues at Rajiv Gandhi Cancer Institute, is the first from India to perform immunophenotypic molecular subtyping of small cell lung cancer (SCLC) using immunohistochemistry (IHC) on 120 unresectable SCLC tissue samples. Traditionally considered a homogeneous disease with poor prognosis, recent molecular analyses have identified four SCLC subtypes based on RNA expression of transcription factors ASCL1, NEUROD1, POU2F3, and YAP1. This study sought to characterize these subtypes at the protein level via IHC and correlate them with response to platinum-based chemotherapy and overall survival (OS).<br /><br />IHC markers used were ASCL1, NEUROD1, POU2F3, YAP1, and the neuroendocrine marker INSM1. Subtypes were defined as ASCL1 dominant, NEUROD1 dominant, POU2F3 positive with negative ASCL1/NEUROD1, and ASCL1/NEUROD1 negative with no POU2F3 expression (NOS). ASCL1 dominant was the most common subtype (58.5%), followed by NEUROD1 dominant (12.1%), POU2F3/ASCL1-/NEUROD1- (7.8%), and ASCL1-/NEUROD1- NOS (21.6%).<br /><br />Key findings included: <br />- NEUROD1 dominant and POU2F3 subtypes showed poor chemotherapy response and more progressive disease (p=0.027).<br />- POU2F3-positive cases lacked neuroendocrine marker expression but exhibited classic SCLC morphology, suggesting POU2F3 can aid diagnosis when traditional neuroendocrine markers are negative.<br />- YAP1 expression varied widely across subtypes and was not definitive for a separate subtype but was associated with poorer overall survival (p=0.013).<br />- Overall survival at one year was 53%, with no significant OS differences among molecular subtypes (p=0.137).<br /><br />The study highlights the utility of IHC in molecular subtyping of SCLC, demonstrating distinct subtypes with potential prognostic and therapeutic implications. Larger multi-institutional studies are needed to further validate these findings and guide tailored treatment strategies.

Asset Subtitle

Sunil Pasricha

Meta Tag

Speaker Sunil Pasricha

Topic Pathology and Biomarkers

Keywords

Small Cell Lung Cancer

Immunophenotypic Molecular Subtyping

Immunohistochemistry

ASCL1

NEUROD1

POU2F3

YAP1

Neuroendocrine Marker INSM1

Chemotherapy Response

Overall Survival