WCLC 2025 - Posters & ePosters-P2.06.11 Factors Impacting Receiving EGFR Test Results Before Initial Treatment Among Stage Iv Non-Small Cell Lung Cancer Patients

P2.06.11 Factors Impacting Receiving EGFR Test Results Before Initial Treatment Among Stage Iv Non-Small Cell Lung Cancer Patients

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This study from India represents the first immunohistochemical (IHC) molecular subtyping of small cell lung carcinoma (SCLC) with correlation to chemotherapy response and prognosis. Traditionally viewed as a homogeneous disease with poor outcomes, recent molecular analyses have identified four SCLC subtypes based on RNA expression of markers ASCL1, NEUROD1, POU2F3, and YAP1. However, protein-level expression data remains limited.<br /><br />The authors performed IHC on formalin-fixed paraffin-embedded tissue from 120 unresectable SCLC patients, assessing expression of ASCL1, NEUROD1, POU2F3, YAP1, and the neuroendocrine marker INSM1. Using defined H-score cutoffs, four subtypes were classified: ASCL1 dominant, NEUROD1 dominant, POU2F3 positive but ASCL1/NEUROD1 negative, and double-negative (ASCL1-/NEUROD1- NOS). Clinical data including platinum-based chemotherapy response and overall survival (OS) were correlated with subtype.<br /><br />Key findings include that ASCL1 dominant was the most common subtype (58.5%), followed by NEUROD1 dominant (12.1%). The POU2F3/ASCL1-/NEUROD1- subtype (7.8%) showed classic SCLC morphology but lacked neuroendocrine marker expression (INSM1 negative), distinguishing it from others. NEUROD1 dominant and POU2F3 subtypes were significantly associated with poor chemotherapy response and progressive disease (p=0.027). YAP1 expression was variable and not definitive of a distinct subtype, but its presence correlated with worse survival (p=0.013). Overall 1-year survival was 53%, with no significant OS difference between molecular subtypes (p=0.137).<br /><br />This study suggests that molecular subtyping by IHC can stratify SCLC into biologically and clinically relevant groups with potential prognostic and therapeutic implications. Particularly, POU2F3 can aid diagnosis in neuroendocrine marker-negative SCLC cases. However, larger multi-institutional studies are needed to validate these findings and clarify their impact on management decisions.

Asset Subtitle

Jeffrey Scott

Meta Tag

Speaker Jeffrey Scott

Topic Pathology and Biomarkers

Keywords

small cell lung carcinoma

SCLC molecular subtyping

immunohistochemistry

ASCL1

NEUROD1

POU2F3

YAP1

chemotherapy response

prognosis

neuroendocrine markers