Fig. 1

Study design and overall review of NSCLC-to-SCLC transformation in this study. A Study flow chart of this study. A total of 1474 NSCLC was reviewed, and 1074 patients were finally analyzed with further treatment in our institution were excluded. 24 cases were confirmed as SCLC transformation out of 343 patients with repeat biopsy, and 8 transformed cases with abundant tumor samples were further sequenced. B Typical images of SCLC transformation cases from lung adenocarcinoma (LUAD). This case presented with morphology of LUAD with positive IHC markers of Napsin A, CK and Vimentin at primary diagnosis before transformation. CT scan indicated tumor progression and the progressed tumor lesion showed morphology of SCLC with high index of Ki-67 and positive expression of Syn, CgA and negative expression of P40 at repeat biopsy (after transformation). C Typical images of SCLC transformation cases from lung squamous carcinoma (LUSC). This case underwent surgical resection and postoperative pathology supported the diagnosis of LUSC with morphological features and positive expression of P63 and negative expression of neuroendocrine marker, CgA at primary diagnosis before transformation. A relapsed tumor was observed on CT scan and the replased tumor showed morphology of SCLC with high index of Ki-67 and positive expression of TTF-1, CgA and Syn at repeat biopsy (after transformation). D Median transformation time in our study was 23.0 months (95%CI, 19.4–26.6). E Overall survival curve of 24 cases after transformation. After transformation developed, the mOS was 9.0 months (95%CI, 7.5–10.6), and the OS of EGFR wild type group was 4.0 months longer than that of EGFR mutant transformation cases (10.0 vs. 6.0 months, P = 0.016). F-H NSE elevation was observed in all transformation cases and representative images of NSE changes during whole disease course. F Comparison of serum NSE before and after SCLC transformation in 24 cases; G-H Dynamic serum NSE change in disease course of representative SCLC transformation cases