ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2020
SCLC Subtypes Defined by ASCL1, NEUROD1, POU2F3, and YAP1: A Comprehensive Immunohistochemical and Histopathologic Characterization.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 315 papers.
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315 citing papers in PubMed, 476 citations in OpenAlex.
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- XPO1-mediated TRIM21 nuclear export reprograms TREM2+ macrophage polarization by targeting IRF3 to augment anti-PD-1 efficacy in small cell lung cancer.Nature communications · 2026Article
- Quantitative Immunohistochemical Landscapes and Chemoimmunotherapy Outcomes of ASCL1, NEUROD1, POU2F3, and YAP1 in Pure Small-Cell Lung Cancer: A Pilot Study.Journal of clinical medicine · 2026Article
- Emerging Therapeutic Strategies in Small-Cell Lung Cancer: From Adaptive Resistance to Precision Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Breast Neuroendocrine Carcinoma: Molecular Insights Beyond Histology.JCO precision oncology · 2026Article
- YAP1 Defines an Emergent, Plastic Population of Relapsed SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Multiplexed quantitative proteomics in small-cell lung cancer: stage-linked DLL3 distribution and an independent prognostic signal of thymidine phosphorylase.Translational lung cancer research · 2026Article
- [Expert Consensus on Immunotherapy for Extensive-stage Small Cell Lung Cancer Based on Molecular Subtyping].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Immunohistochemical profiling of small cell lung cancer reveals subtype heterogeneity and a tuft cell-like subtype characterized by LRMP and TRPM5.Virchows Archiv : an international journal of pathology · 2026Article
255 more citing papers are in PubMed but not listed here.
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19 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionRecent studies have identified subtypes of small cell lung carcinoma (SCLC) defined by the RNA expression of ASCL1, NEUROD1, POU2F3, and YAP1 transcriptional regulators. There are only limited data on the distribution of these markers at the protein level and associated pathologic characteristics in clinical SCLC samples.
methodsThe expression of ASCL1, NEUROD1, POU2F3, and YAP1 was analyzed by immunohistochemistry in 174 patient samples with SCLC. Subtypes defined by these markers were correlated with histologic characteristics, expression of classic neuroendocrine markers (synaptophysin, chromogranin A, CD56, INSM1), and other SCLC markers, including the neuroendocrine phenotype-associated markers TTF-1 and DLL3.
resultsASCL1 and NEUROD1 expression had the following distribution: (1) 41% ASCL1+/NEUROD1-; (2) 37% ASCL1+/NEUROD1+; (3) 8% ASCL1-/NEUROD1+; and (4) 14% ASCL1-/NEUROD1-. On the basis of their relative expression, 69% of cases were ASCL1-dominant and 17% were NEUROD1-dominant. POU2F3 was expressed in 7% of SCLC and was mutually exclusive of ASCL1 and NEUROD1. YAP1 was expressed at low levels, primarily in combined SCLC, and was not exclusive of other subtypes. Both ASCL1-dominant and NEUROD1-dominant subtypes were associated with neuroendocrine marker
conclusionsThis is the first comprehensive immunohistochemical and histopathologic analysis of novel SCLC subtypes in patient samples. We confirm that ASCL1/NEUROD1 double-negative tumors represent a distinct neuroendocrine-low subtype of SCLC, which is either uniquely associated with POU2F3 or lacks a known dominant regulator. The expression profiles of these markers appear more heterogeneous in native samples than in experimental models, particularly with regard to the high prevalence of ASCL1/NEUROD1 coexpression. These findings may have prognostic and therapeutic implications and warrant further clinical investigation.
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