Fibroblast growth factor receptor 1 gene amplification is associated with poor survival in patients with resected esophageal squamous cell carcinoma

Abstract

To investigate the frequency and the prognostic impact of fibroblast growth factor receptor 1 (FGFR1) gene amplification in 526 curatively resected esophageal squamous cell carcinoma (ESCC). Using fluorescent in situ hybridization, high amplification was defined by an FGFR1/centromer 8 ratio is ≥ 2.0, or average number of FGFR1 signals/tumor cell nucleus ≥ 6.0, or percentage of tumor cells containing ≥ 15 FGFR1 signals or large cluster in ≥ 10%. Low amplification was defined by ≥ 5 FGFR1 signals in ≥ 50%. FGFR2 and FGFR3 mutations were assessed by direct sequencing in 388 cases and no mutation was detected. High and low amplification were detected in 8.6% and 1.1%, respectively. High FGFR1 amplification had significantly shorter disease-free survival (34.0 vs 158.5 months P=0.019) and overall survival (52.2 vs not reached P=0.022) than low/no amplification group. After adjusting for sex, smoking, stage, histology, and adjuvant treatment, high FGFR1 amplification had a greater risk of recurrence (adjusted hazard ratio [AHR], 1.6; P=0.029) and death (AHR, 1.53; P=0.050). High amplification was significantly higher in current smokers than former and never-smokers (Ptrend<0.001) and increased proportional to smoking dosage. High FGFR1 amplification is a frequent oncogenic alteration and an independent poor prognostic factor in resected ESCC.

Prognostic implications of Fibroblast growth factor receptor 1 (FGFR1) gene amplification and protein overexpression in hypopharyngeal and laryngeal squamous cell carcinoma

“…FGFR1 gene amplification was observed in about 12% tested hypopharyngeal and laryngeal SCC cases that was slightly more frequent in hypopharyngeal SCC (14.3%) Variables of the pT and pN classification were not included in the multivariate analysis, because they were included in the pathologic stage than in laryngeal SCC (8.3%). FGFR1 amplification has been suggested as an oncogenic driver mutation in tobacco-associated cancers of the aerodigestive tract [16,[32][33][34]. Previous studies on FGFR1 in HNSCC have shown that FGFR1 amplification is more common in the SCC of hypopharynx and larynx than in that of oropharynx or oral cavity [14,16].…”

Different clinical significance of FGFR1–4 expression between diffuse-type and intestinal-type gastric cancer

“…FGFR1 protein expression of ≥1% in tumors was associated with poor survival in patients with breast cancer [35]. FGFR1 amplification was also associated with poor survival in esophageal cancer [36], breast cancer [37], and squamous-cell lung cancer [38]. In a study of colorectal cancer, the copy number gain of FGFR1 significantly correlated with worse outcomes [39].…”

Prognostic implications ofFGFR1andMYCstatus in esophageal squamous cell carcinoma

“…Several previous studies reported the prognostic implication of FGFR1 amplification in ESCC, but the results were controversial[11,12]. FGFR1 amplification was associated with poor prognosis or had no prognostic significance in ESCC; however, the FISH criteria for FGFR1 amplification were not identical[11,12].…”

“…FGFR1 amplification was associated with poor prognosis or had no prognostic significance in ESCC; however, the FISH criteria for FGFR1 amplification were not identical[11,12]. In the present study, FGFR1 amplification was a favorable prognostic indicator in patients with resected ESCC, which was in conflict with a previous report using the same FISH criteria[11]. In a study using FISH and different criteria, FGFR1 amplification was not associated with clinical outcomes in patients with ESCC[12].…”

“…Additionally, new drugs targeting FGFR and its related pathways, including multi-kinase inhibitors and selected FGFR inhibitors, have been introduced for cancer treatment[5,10]. However, the prognostic significance of FGFR1 amplification in patients with ESCC remains controversial[11,12]. …”