{"entity":{"id":"paper-baine-sclc-subtype-immunohistochemistry-jto-2020","kind":"paper","name":"SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization","aka":[],"tldr":"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.","asOf":"2026-09-25","links":[{"label":"Baine et al., J Thorac Oncol 2020: immunohistochemical characterisation of the small-cell subtypes in 174 patient samples","url":"https://doi.org/10.1016/j.jtho.2020.09.009"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33011388/"}],"tags":[],"related":["dll3-expression"],"cancers":["sclc"],"sections":[],"technologies":["histopathology-ihc"],"targets":["ascl1","yap1","dll3","nkx2-1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["sclc-signalling","lineage-plasticity-neuroendocrine","notch"],"terms":["ihc"],"trials":[],"people":["charles-rudin"],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2020,"doi":"10.1016/j.jtho.2020.09.009","pmid":"33011388","authors":"Baine MK, Hsieh MS, Lai WV, et al.","paperType":"observational","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."],"whatItMeans":"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."],"changedPractice":false,"participants":174},"route":"/key-papers/paper-baine-sclc-subtype-immunohistochemistry-jto-2020/","neighbours":{"biomarker":[{"id":"dll3-expression","kind":"biomarker","name":"DLL3 expression","route":"/biomarkers/dll3-expression/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"ascl1","kind":"target","name":"ASCL1","route":"/targets/ascl1/"},{"id":"dll3","kind":"target","name":"DLL3","route":"/targets/dll3/"},{"id":"nkx2-1","kind":"target","name":"NKX2-1","route":"/targets/nkx2-1/"},{"id":"yap1","kind":"target","name":"YAP1","route":"/targets/yap1/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"notch","kind":"pathway","name":"Notch signalling","route":"/pathways/notch/"},{"id":"sclc-signalling","kind":"pathway","name":"Small cell lung cancer (KEGG map)","route":"/pathways/sclc-signalling/"}],"term":[{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"}],"person":[{"id":"charles-rudin","kind":"person","name":"Charles M. Rudin","route":"/people/charles-rudin/"}],"journal":[{"id":"journal-of-thoracic-oncology","kind":"journal","name":"Journal of Thoracic Oncology","route":"/journals/journal-of-thoracic-oncology/"}]}}