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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.
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.
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.
Shares ASCL1, DLL3 expression, YAP1, Charles M. Rudin.
Shares ASCL1, YAP1, Small cell lung cancer (KEGG map), DLL3.
Shares Charles M. Rudin, Journal of Thoracic Oncology, Lineage plasticity & neuroendocrine transformation, Memorial Sloan Kettering Cancer Center.
Shares DLL3 expression, DLL3, Immunohistochemistry (IHC), Small-cell lung cancer.
Shares Lineage plasticity & neuroendocrine transformation, Immunohistochemistry (IHC), Histopathology & immunohistochemistry, Small-cell lung cancer.
Shares Journal of Thoracic Oncology, Immunohistochemistry (IHC), Histopathology & immunohistochemistry, Non-small-cell lung cancer.
Shares Journal of Thoracic Oncology, Immunohistochemistry (IHC), Histopathology & immunohistochemistry, Non-small-cell lung cancer.
Shares Journal of Thoracic Oncology, Memorial Sloan Kettering Cancer Center, Non-small-cell lung cancer.