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Published on: October 21, 2022
Fibroblast growth factor receptor 1 gene amplification and protein expression in human lung cancer
Omar Elakad1, Anna-Maria Lois1, Katja Schmitz1
1Institute of Pathology, University Medical Center, Göttingen, Germany.
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 results regarding the impact of FGFR1 amplification and expression on patient's prognosis.
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 & 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.
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.
Insights
Fibroblast growth factor receptor 1 (FGFR1) amplification and expression do not impact lung cancer patient survival. Current patient selection for FGFR1 inhibitors may need reconsideration based on these findings.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeting fibroblast growth factor receptor 1 (FGFR1) shows promise for squamous cell lung cancer (SQCLC).
- Current treatment decisions rely on FGFR1 gene amplification, but durable responses are limited.
- Previous research on FGFR1's prognostic impact in lung cancer yields conflicting results.
Purpose of the Study:
- To investigate the prevalence and correlation of FGFR1 gene amplification and protein expression in lung cancer.
- To determine the impact of FGFR1 amplification and expression on overall survival.
- To evaluate the relationship between FGFR1 amplification, expression, and clinicopathological characteristics.
Main Methods:
- Analyzed FGFR1 gene amplification using fluorescence in situ hybridization in 208 SQCLC and 45 small cell lung cancers (SCLC).
- Assessed FGFR1 protein expression via immunohistochemistry in SQCLC, SCLC, and 121 pulmonary adenocarcinomas (ACs).
- Correlated amplification and expression with clinicopathological features and overall survival.
Main Results:
- FGFR1 amplification occurred in 23% of SQCLC and 8% of SCLC, correlating with male patients but not survival.
- Strong FGFR1 expression was observed in 9% of SQCLC, 35% of ACs, and 4% of SCLCs, correlating with females and absence of lymph node metastasis in SQCLC, but not survival.
- No significant correlation was found between FGFR1 gene amplification and protein expression.
Conclusions:
- FGFR1 gene amplification does not correlate with its protein expression in lung cancer.
- Neither FGFR1 amplification nor protein expression appears to influence patient prognosis.
- Patient selection for FGFR1 inhibitors warrants re-evaluation.
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