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

Medientyp: E-Artikel
Titel: Fibroblast growth factor receptor 1 gene amplification and protein expression in human lung cancer
Beteiligte: Elakad, Omar; Lois, Anna‐Maria; Schmitz, Katja; Yao, Sha; Hugo, Sara; Lukat, Laura; Hinterthaner, Marc; Danner, Bernhard C.; von Hammerstein‐Equord, Alexander; Reuter‐Jessen, Kirsten; Schildhaus, Hans‐Ulrich; Ströbel, Philipp; Bohnenberger, Hanibal
Erschienen: Wiley, 2020
Erschienen in: Cancer Medicine
Umfang: 3574-3583
Sprache: Englisch
DOI: 10.1002/cam4.2994
ISSN: 2045-7634
Schlagwörter: Cancer Research ; Radiology, Nuclear Medicine and imaging ; Oncology
Zusammenfassung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Targeting fibroblast growth factor receptor 1 (<jats:italic>FGFR1</jats:italic>) 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 results regarding the impact of <jats:italic>FGFR1</jats:italic> amplification and expression on patient's prognosis.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>Here, we analyzed prevalence and correlation of <jats:italic>FGFR1</jats:italic> gene amplification and protein expression in human lung cancer and their impact on overall survival.</jats:p></jats:sec><jats:sec><jats:title>Materials & Methods</jats:title><jats:p><jats:italic>FGFR1</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic>FGFR1</jats:italic> was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (<jats:italic>P</jats:italic> = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 <jats:italic>FGFR1</jats:italic> knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (<jats:italic>P</jats:italic> = .0187) and to the absence of lymph node metastasis in SQCLC (<jats:italic>P</jats:italic> = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p><jats:italic>FGFR1</jats:italic> gene amplification does not seem to correlate to protein expression.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We believe that patient selection for <jats:italic>FGFR1</jats:italic> inhibitors in clinical studies should be reconsidered. Neither <jats:italic>FGFR1</jats:italic> amplification nor expression influences patient's prognosis.</jats:p></jats:sec>
Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Targeting fibroblast growth factor receptor 1 (<jats:italic>FGFR1</jats:italic>) 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 results regarding the impact of <jats:italic>FGFR1</jats:italic> amplification and expression on patient's prognosis.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>Here, we analyzed prevalence and correlation of <jats:italic>FGFR1</jats:italic> gene amplification and protein expression in human lung cancer and their impact on overall survival.</jats:p></jats:sec><jats:sec><jats:title>Materials & Methods</jats:title><jats:p><jats:italic>FGFR1</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic>FGFR1</jats:italic> was amplified in 23% of SQCLC and 8% of SCLC. Amplification was correlated to males (<jats:italic>P</jats:italic> = .027) but not to overall survival. Specificity of immunostaining was verified by cellular CRISPR/Cas9 <jats:italic>FGFR1</jats:italic> knockout. FGFR1 was strongly expressed in 9% of SQCLC, 35% of AC, and 4% of SCLC. Expression was correlated to females (<jats:italic>P</jats:italic> = .0187) and to the absence of lymph node metastasis in SQCLC (<jats:italic>P</jats:italic> = .018) with no significant correlation to overall survival. Interestingly, no significant correlation between amplification and expression was detected.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p><jats:italic>FGFR1</jats:italic> gene amplification does not seem to correlate to protein expression.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We believe that patient selection for <jats:italic>FGFR1</jats:italic> inhibitors in clinical studies should be reconsidered. Neither <jats:italic>FGFR1</jats:italic> amplification nor expression influences patient's prognosis.</jats:p></jats:sec>
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