# SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization

Source: https://onco.cc/key-papers/paper-baine-sclc-subtype-immunohistochemistry-jto-2020/  
OnCo record `paper-baine-sclc-subtype-immunohistochemistry-jto-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The four kinds of small-cell lung cancer were defined in laboratory models. Staining 174 real patient samples showed the picture is messier: more than a third of tumours switch on two of the control proteins at once.

## Summary

Expression of ASCL1, NEUROD1, POU2F3 and YAP1 was analysed by immunohistochemistry in 174 patient samples of small-cell lung carcinoma and correlated with histological characteristics, classic neuroendocrine markers and other markers including TTF-1 and DLL3. ASCL1 and NEUROD1 expression distributed as 41% ASCL1-positive and NEUROD1-negative, 37% positive for both, 8% ASCL1-negative and NEUROD1-positive, and 14% negative for both; on relative expression, 69% were ASCL1-dominant and 17% NEUROD1-dominant. POU2F3 was expressed in 7% and was mutually exclusive of ASCL1 and NEUROD1. YAP1 was expressed at low levels, primarily in combined small-cell carcinomas, and was not exclusive of other subtypes. ASCL1-dominant and NEUROD1-dominant tumours had a neuroendocrine marker high, TTF-1 high and DLL3 high profile, whereas POU2F3 and other double-negative tumours were low for all three.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Journal of Thoracic Oncology
- Year: 2020
- DOI: 10.1016/j.jtho.2020.09.009
- Authors: Baine MK, Hsieh MS, Lai WV, et al.
- Findings: 69% of tumours are ASCL1-dominant and 17% NEUROD1-dominant, with 37% expressing both.; POU2F3 is expressed in 7% and is mutually exclusive of the other two.; YAP1 is low and not exclusive, mostly in combined small-cell carcinomas.; POU2F3 and double-negative tumours are low for neuroendocrine markers, TTF-1 and DLL3.
- What it means: It is the reality check on the subtype model and it has a direct consequence for treatment: the DLL3-directed medicines are aimed at the neuroendocrine-high subtypes, and the POU2F3 and double-negative tumours will not express the target.
- Caveats: Immunohistochemistry is a coarse readout of a transcriptional state.; Single-institution samples, many from small biopsies.; Co-expression of ASCL1 and NEUROD1 in 37% means dominance has to be defined by relative intensity, which is subjective.

## Sources

- Baine et al., J Thorac Oncol 2020: immunohistochemical characterisation of the small-cell subtypes in 174 patient samples: https://doi.org/10.1016/j.jtho.2020.09.009
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33011388/

## Connected records

- biomarkers: [DLL3 expression](https://onco.cc/biomarkers/dll3-expression/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [ASCL1](https://onco.cc/targets/ascl1/), [DLL3](https://onco.cc/targets/dll3/), [NKX2-1](https://onco.cc/targets/nkx2-1/), [YAP1](https://onco.cc/targets/yap1/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/), [Notch signalling](https://onco.cc/pathways/notch/), [Small cell lung cancer (KEGG map)](https://onco.cc/pathways/sclc-signalling/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- people: [Charles M. Rudin](https://onco.cc/people/charles-rudin/)
- journals: [Journal of Thoracic Oncology](https://onco.cc/journals/journal-of-thoracic-oncology/)

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