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

Abstract

Background: The gene encoding fibroblast growth factor receptor 1 (FGFR1) is emerging as a therapeutic and prognostic biomarker in various cancer types, including head and neck squamous cell carcinoma (SCC). Here, we investigated the clinicopathologic implication of FGFR1 gene amplification and protein overexpression in hypopharyngeal and laryngeal SCC.Methods: Fluorescence in situ hybridization and immunohistochemistry were performed to determine FGFR1 gene amplification and protein overexpression in 209 surgically resected cases. Results: FGFR1 amplification observed in 8 (8/66, 12.1%; 6 hypopharynx and 2 larynx) patients and high FGFR1 expression in 21 (21/199, 10.6%) patients significantly correlated with lymph node metastasis and advanced pathological stages. FGFR1 amplification was also associated with worse disease-free survival in multivariate analysis (hazard ratio = 4.527, P = 0.032). High FGFR1 expression was more frequently observed, consistent with the worsening of the degree of histologic differentiation.Conclusions: FGFR1 amplification may serve as an independent prognostic factor for disease-free survival in hypopharyngeal and laryngeal SCC. Aberrant FGFR signaling caused by FGFR1 gene amplification or protein overexpression may play a crucial role in the malignant evolution and progression of hypopharyngeal and laryngeal SCC, and offer novel therapeutic opportunities in patients with hypopharyngeal and laryngeal SCC that usually lack specific therapeutic targets.

Prognostic value of FGFR1 expression and amplification in patients with HNSCC: A systematic review and meta-analysis

“…Hase et al , Young et al and Koole et al reported that FGFR1 was associated with poor outcome of HNSCC [ 17 , 31 – 33 ]. Kim et al recently found that FGFR1 amplification may serve as an independent prognostic factor for DFS in hypopharyngeal and laryngeal squamous cell carcinoma [ 34 ]. Our results are consistent with these results.…”

Long non‑coding RNA HCG18 facilitates the progression of laryngeal and hypopharyngeal squamous cell carcinoma by upregulating FGFR1 via miR‑133b

“…In recent years, the upregulation of FGFR1 has been found in breast cancer, ovarian cancer and tongue squamous cell carcinoma ( 28 – 30 ). Similarly, the amplification of FGFR1 may serve as an independent prognostic factor for disease-free survival in LHSCC ( 31 ). Related studies have shown that HCG18 promoted the progression of lung adenocarcinoma by regulating miR-34a-5p-mediated hyaluronan mediated motility receptor expression ( 12 ).…”

Therapeutic Targeting of FGFR Signaling in Head and Neck Cancer

“…Multiple studies demonstrated that FGFR1 overexpression is related to poor prognosis in HPV-negative HNSCC patients, 31,33,34 whereas others suggest the contrary. 26,29,35 The perceived discrepancy may be attributed to a number of factors, including the difference in the cutoff value for FGFR1 expression, various anatomic positions of HNSCC, different sample size, and distinct patient ethnicities from different studies. In line with this suggestion, Fisher and colleagues 32 reported that the sensitivity of AZD4547, a selective FGFR inhibitor, is not associated with FGFR expression level in a panel of 10 HNSCC cell lines they examined, including both HPV-positive and HPV-negative cells.…”

“…However, at present, conflicting results in terms of FGFR1 expression as a prognosis biomarker have been reported. Multiple studies demonstrated that FGFR1 overexpression is related to poor prognosis in HPV-negative HNSCC patients, 31,33,34 whereas others suggest the contrary 26,29,35 . The perceived discrepancy may be attributed to a number of factors, including the difference in the cutoff value for FGFR1 expression, various anatomic positions of HNSCC, different sample size, and distinct patient ethnicities from different studies.…”