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Background  We aimed to investigate prevalence and prognostic role of  SOX2, PIK3CA, FGFR1  and  BRF2  gene gain in patients with surgically resected non-small cell lung cancer (NSCLC).    Methods    SOX2, PIK3CA, FGFR1  and  BRF2  gene copy number was assessed by fluorescence  in situ  hybridization (FISH) in arrayed tissue cores from 447 resected NSCLCs.    Results  Increased gene copy number (FISH+) for  SOX2 ,  PIK3CA ,  FGFR1  and  BRF2  was observed in 23.6%, 29.2%, 16.6% and 14.9% of cases, respectively. FISH+ status for each gene was significantly associated with smoking history, squamous cell carcinoma (SCC) histology, and increased copy number of the other studied genes. Multivariate analysis of overall survival indicated increased  SOX2  gene copy number ( P  = 0.008), stage I-II ( P <0.001), and adenocarcinoma or SCC histology ( P  = 0.016) as independent, favorable prognostic factors. A statistically significant interaction was observed between stage and  SOX2  gene status ( P  = 0.021), indicating that the prognostic impact of  SOX2  gene gain differs across stages and is limited to patients with stage I-II disease (HR 0.44, 95% CI: 0.25–0.77;  P  = 0.004, adjusted for histology).    Conclusions  Increased SOX2 gene copy number is an independent and favorable prognostic factor in surgically resected, early stage NSCLC, regardless of histology. SOX2, PIK3CA, FGFR1 and BRF2 gene gains are likely to occur concurrently, with potentially relevant implications for the development of new therapeutic strategies.

plos one

Increased SOX2 Gene Copy Number Is Associated with FGFR1 and PIK3CA Gene Gain in Non-Small Cell Lung Cancer and Predicts Improved Survival in Early Stage Disease