FGFR1 amplification predicts poor outcome in early-stage NSCLC

Amplification of fibroblast growth factor receptor 1 (FGFR1) is associated with poor clinical outcome in patients with early-stage non-small-cell lung cancer (NSCLC), Swiss researchers report.

Coya Tapia, from the University of Bern, and colleagues used fluorescence in situ hybridisation to measure FGFR1 amplification in tissue samples from 329 patients with early-stage (IA–IIB), node-negative NSCLC treated with curative surgery.

They chose to investigate this marker because it has recently been described as “a promising predictive marker for anti-FGFR inhibitor treatment.”

As reported in the British Journal of Cancer, the overall prevalence of FGFR1 amplification was 12.5%, and was significantly higher in 169 samples taken from patients with squamous cell carcinoma (SCC) than in those taken from 137 patients with adenocarcinoma and 23 patients with large cell carcinoma (20.7 vs 2.2 and 13.0%, respectively).

FGFR1 amplification increased significantly with increasing T category, and was not detected in any of the 36 samples classified as T1. FGFR1 amplification was also associated with larger tumour size and higher tumour stage.

This finding contradicts an earlier hypothesis that FGFR1 amplification is a driver mutation, the researchers note. They suggest, instead, that the amplification is a passenger mutation that is acquired later during tumour growth.

Tapia and team also found that FGFR1 amplification mainly occurred in male smokers or ex-smokers. They say that this is unsurprising because most SCCs are diagnosed in men with a smoking history. “Whether smoking causes FGFR1 alterations or whether smoking and FGFR1 alterations are independent and trigger combined tumorigenesis in NSCLC has to be determined in further studies”, they remark.

Patients with FGFR1 amplification had significantly worse overall survival and disease-free survival than those without it, at a median of 43.9 versus 103.1 months and 22.5 versus 52.4 months, respectively.

Furthermore, multivariate analysis adjusted for smoking status, tumour size and pathological tumour stage confirmed that FGFR1 amplification was independently associated with prognosis. Indeed, those with the amplification were twice as likely to die during follow-up as those without it.

When the researchers looked specifically at SCC they observed significantly worse overall survival among tumours with FGFR1 amplification during the first 4 years, but no significant difference after this time, possibly because all patients with an aggressive, FGFR1-amplified tumour died early, they suggest.

Tapia and co-authors conclude that, while FGFR1 amplification appears to be a prognostic marker in early-stage NSCLC, further studies are needed to determine its value as a predictive marker for targeted therapies or adjuvant treatment.

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