Figure 6.

Primary and secondary SCLC within the network of NE lung carcinomas. (a) Four special lung carcinoma cases were selected for comprehensive NGS, IHC and FISH analysis. Case 1 – LCNEC, Case 2 – primary SCLC with combined AdC and SqCC, Case 3 – NE AdC combined with non‐NE AdC, Case 4 – secondary SCLC with combined AdC as relapse of TKI‐treated AdC. Corresponding IHC data are presented in Supporting Information Figure S7. (b) Primary SCLC (2) is suggested to arise from cancer stem cells out of a NE niche upon bi‐allelic loss of TP53 and RB1. Secondary SCLC (4) may originate from non‐NE cancer stem cells that acquire NE differentiation through inactivating NOTCH mutations and additionally a bi‐allelic loss of TP53 and RB1. Intermediate tumor stages as NE differentiated NSCLC (3) or LCNEC (1) depend on the mutation status of TP53 and RB1.