Fibroblast growth factor receptor 1 gene amplification and protein expression in human lung cancer

人肺癌中成纤维细胞生长因子受体1基因扩增和蛋白质表达

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作者:Omar Elakad, Anna-Maria Lois, Katja Schmitz, Sha Yao, Sara Hugo, Laura Lukat, Marc Hinterthaner, Bernhard C Danner, Alexander von Hammerstein-Equord, Kirsten Reuter-Jessen, Hans-Ulrich Schildhaus, Philipp Ströbel, Hanibal Bohnenberger

Aims

Here, we analyzed prevalence and correlation of FGFR1 gene amplification and protein expression in human lung cancer and their impact on overall survival. MATERIALS &

Background

Targeting fibroblast growth factor receptor 1 (FGFR1) is a potential treatment for squamous cell lung cancer (SQCLC). So far, treatment decision in clinical studies is based on gene amplification. However, only a minority of patients have shown durable response. Furthermore, former studies have revealed contrasting

Conclusion

We believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis.

Discussion

FGFR1 gene amplification does not seem to correlate to protein expression. Conclusion: We believe that patient selection for FGFR1 inhibitors in clinical studies should be reconsidered. Neither FGFR1 amplification nor expression influences patient's prognosis.

Methods

FGFR1 gene amplification and protein expression were analyzed by fluorescence in situ hybridization and immunohistochemistry (IHC) in 208 SQCLC and 45 small cell lung cancers (SCLC). Furthermore, FGFR1 protein expression was analyzed in 121 pulmonary adenocarcinomas (ACs). Amplification and expression were correlated to each other, clinicopathological characteristics, and overall survival.

Results

FGFR1 was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (P = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 FGFR1 knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (P = .0187) and to the absence of lymph node metastasis in SQCLC (P = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected.

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